Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
In a pilot clinical trial published in the Journal of the American Geriatrics Society that included older adults with depression receiving standard care, adding probiotic therapy produced modest but meaningful reductions in depressive and anxiety symptoms compared with adding a placebo. However, both groups demonstrated substantial overall improvements during follow-up.
For the trial, 58 participants in India aged ≥ 60 years with moderate depression were randomised 1:1 to receive daily probiotics or a placebo for 12 weeks, alongside standard antidepressant care. They were followed up for another 12 weeks.
Based on validated psychological scores, biomarker (serum brain-derived neurotropic factor level), and faecal microbiota profiling, investigators found that probiotics helped improve patients’ symptoms but did not confer clear additional gains in quality of life compared with placebo. The findings support probiotics as a safe, biologically plausible adjunct to standard care, but larger trials are needed.
“The results of our study are novel, and we are now planning a follow-up, larger-scale clinical trial due to the encouraging findings,” said co-corresponding author Dr. Saibal Das, MBBS, MD, DM, PhD, of the Indian Council of Medical Research – National Institute for Research in Bacterial Infections, Kolkata. “My vision is to develop affordable healthcare solutions and make them available to the larger population for meaningful public health impact,” added co–corresponding author Abhinaba Ghosh, MBBS, MSc, PhD, a physician-neuroscientist from Tata Medical Center, Kolkata.
When it comes to autism, few questions spark as much debate as how best to support autistic people with the greatest needs.
This prompted The Lancet medical journal to commission a group of international experts to propose a new category of “profound autism”.
This category describes autistic people who have little or no language (spoken, written, signed or via a communication device), who have an IQ of less than 50, and who require 24-hour supervision and support.
It would only apply to children aged eight and over, when their cognitive and communication abilities are considered more stable.
In our new study, we considered how the category could impact autism assessments. We found 24% of autistic children met, or were at risk of meeting, the criteria for profound autism.
Why the debate?
The category is intended to help governments and service providers plan and deliver supports, so autistic people with the highest needs aren’t overlooked. It also aims to re-balance their under-representation in mainstream autism research.
This new category may be helpful for advocating for a greater level of support, research and evidence for this group.
But some have raised concerns that autistic people who don’t fit into this category could be perceived as less in need and excluded from services and funding supports.
Others argue the category doesn’t sufficiently emphasise autistic people’s strengths and capabilities, and places too much emphasis on the challenges that are experienced.
What did we do?
We conducted the first Australian study to examine how the “profound autism” category might apply to children attending publicly funded diagnostic services for developmental conditions.
Drawing on the Australian Child Neurodevelopment Registry, we examined data from 513 autistic children assessed between 2019 and 2024. We asked:
how many children met the criteria for profound autism?
were there behavioural features that set this group apart?
Because we focused on children at the time of diagnosis, most (91%) were aged under eight years. We described these children as being “at risk of profound autism”.
What did we find?
Around 24% of autistic children in our study met, or were at risk of meeting, the criteria for profound autism. This is similar to the proportion of children internationally.
Almost half (49.6%) showed behaviours that were a safety risk, such as attempting to run away from carers, compared with one-third (31.2%) of other autistic children.
These challenges weren’t limited to children who met criteria for profound autism. Around one in five autistic children (22.5%) engaged in self-injury, and more than one-third (38.2%) showed aggression toward others.
So, while the category identified many children with very high needs, other children who didn’t meet these criteria also had significant needs.
Importantly, we found the definition of “profound autism” doesn’t always line up with the official diagnostic levels which determine the level of support and NDIS funding children receive.
In our study, 8% of children at risk of profound autism were classified as level 2, rather than level 3 (the highest level of support). Meanwhile, 17% of children classified as level 3 did not meet criteria for profound autism.
Our concern
We looked at children when they first received an autism diagnosis. Children were aged 18 months to 16 years, with more than 90% under the age of eight years.
This aligns with our earlier research, showing the average age of diagnosis in public settings is 6.6 years.
From a practical perspective, our biggest concern about the profound autism category is the age threshold of eight years.
Because most children are already assessed before age eight, introducing this category into assessment services would mean many families would need repeat assessments, placing additional strain on already stretched developmental services.
Second, modifications will be needed if this criteria is going to be used to inform funding decisions as it didn’t map perfectly onto level 3 support criteria.
On balance, however, our results suggest the profound autism category may provide a clear, measurable way to describe the needs of autistic people with the highest support requirements.
Every autistic child has individual strengths and needs. The term “profound autism” would need to be promoted with inclusive and supportive language, so as to not replace or diminish individual needs, but to help clinicians tailor supports and obtain additional resources when needed.
If you’re concerned your child requires substantial support, here are some practical steps you can take to ensure their needs are recognised and addressed:
Explain your concerns
Not all clinicians have experience working with children with high support needs. Be as clear as possible about behaviours that affect your child’s safety or daily life, including self-injury, aggression or attempts to run away. These details, while difficult to share, help give a clearer picture of your child’s support needs.
It can also be a challenge to find and access clinicians with appropriate expertise. Another potential benefit of having a defined category is that it can better help families navigate care.
Ask about support for the whole family
Our studies show that many caregivers want more support for themselves but don’t always ask. Talk with clinicians about supports for yourself as well, including respite, or family support groups.
Reach out
Coming together with other carers and families can reduce your own isolation and normalise many of the unique challenges you face. Connecting with like-minded people can provide a supportive, empathetic and empowering community.
Plan for safety
For children with high support needs, prioritise safety planning with your child’s care team. This can include strategies to reduce risks, as well as planning how best to support your child’s interactions with health, education and disability services over time.
For many people who suffer from depression, the condition is not just about feeling down, but also about a loss of motivation and difficulty finding pleasure in activities they used to enjoy. A study conducted in Sweden at Lund University and Region Skåne shows that a medicine used to treat Parkinson’s disease can be used as an add-on therapy to alleviate these symptoms in some patients with treatment-resistant depression.
Researchers at Lund University and the psychiatric services in Region Skåne have identified a potential new therapy for the condition associated with depression that involves a reduced ability to feel joy, pleasure or motivation – known as anhedonia. Those affected may lose interest in things that they previously found meaningful or rewarding.
The study is an example of what is known as drug repurposing, whereby an already approved medicine is used to treat a different condition. In this study, the researchers investigated pramipexole, which has long been used to treat Parkinson’s disease, as an add-on therapy for depression with marked anhedonia.
“Anhedonia is one of the most debilitating symptoms of depression, and something on which current antidepressant therapies often have only a limited effect. Our findings suggest that pramipexole could be an important new therapy option for this patient group,” says Daniel Lindqvist, a researcher at Lund University and senior consultant in psychiatry at Region Skåne.
All participants in the study had marked anhedonia. Patients were given either pramipexole or a placebo as an add-on to their ongoing medication for nine weeks.
“Those treated with pramipexole for anhedonia showed a more pronounced improvement compared with the placebo group. The effect persisted during a six-month follow-up period among those patients who chose to continue treatment,” says Daniel Lindqvist.
The researchers used advanced brain imaging techniques (7 Tesla fMRI) to investigate the possible biological mechanisms underlying the effect, and activity monitors to assess whether the therapy affected patients’ everyday movement and activity levels.
“We found that pramipexole was linked to a positive effect on the brain’s reward system and increased physical activity in everyday life. This supports the theory that the drug affects the dopamine system, which plays a key role in motivation and reward processing,” says Filip Ventorp, a postdoc at Lund University and resident physician at Region Skåne.
Most patients experienced no major issues with the treatment, and few patients dropped out during the randomized controlled trial. Common side effects included sleep problems, nausea and dizziness, but these could usually be managed by adjusting the dose. Even those who chose to continue with the follow-up phase of the study for a further six months generally responded well to the therapy.
“Efficacy and safety were maintained over time during the follow-up phase, which is particularly relevant in cases of long-term and treatment-resistant depression. Although most participants in our study tolerated the drug well, it is important to monitor any side effects, such as impaired impulse control and daytime fatigue,” says Marie Asp, a psychiatric researcher at Lund University and senior consultant in psychiatry at Region Skåne.
A circuit that runs from the prefrontal cortex near the front of the brain to a deeper brain structure called the insular cortex appears to mediate the antidepressant effects of a newer form of transcranial magnetic stimulation (TMS), according to a study led by Weill Cornell Medicine investigators. The discovery could lead to more effective TMS treatment of depression.
In the study, published May 7 in Cell, the researchers developed mice whose brains can be stimulated artificially in a prefrontal region to mimic the antidepressant effect of a widely used—but not well understood—TMS technique. The researchers showed that this antidepressant effect in the mice depends heavily on the indirect stimulation of a connected region, the insular cortex.
“We’re excited about this work because it advances our understanding of the antidepressant effects of TMS, and points to more effective ways of delivering this therapy,” said study senior author Dr. Conor Liston, the Robert Michels, M.D. Professor of Psychiatry in the Department of Psychiatry and a professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. Dr. Shane B. Johnson, Dr. Devin Rocks and Dr. Laura Chalencon, postdoctoral associates in psychiatry at the time of the study, were co-first authors of the study.
Depression is one of the most commonly diagnosed illnesses in the modern world, and its prevalence has been increasing in recent decades. In the United States alone, tens of millions of people are treated for depression annually, according to the National Institute of Mental Health. Antidepressant drugs called selective serotonin reuptake inhibitors are the most common treatments but can take weeks to work and frequently have side effects.
TMS treatments, though they involve clinic visits, have the advantage of being more targeted, with few if any side effects, and are increasingly used for patients who do not respond to drug therapy. One new TMS protocol called accelerated intermittent theta-burst stimulation (aiTBS) has been found to reduce or abolish depression symptoms in many patients after only a few days of treatment. But exactly how TMS works and how it could be optimized have been notoriously difficult to study.
“There’s a lot of variation in how you can deliver TMS, which makes it very hard to test systematically in humans,” said Dr. Liston, who is also a psychiatrist at NewYork-Presbyterian/Weill Cornell Medical Center. “The variables include the duration of treatment in each session, the specific pulse rhythm, the interval between sessions and the specific brain area targeted, among others.”
The researchers developed a mouse model to explore and optimize aiTBS. The optogenetic mouse model allows the researchers to use light pulses to stimulate specific groups of neurons, with the same rhythms used in aiTBS. The team showed that stimulating the same prefrontal region targeted by aiTBS reverses stress-induced, depression-like behaviors in the mice.
Next, the scientists identified the specific prefrontal neurons that mediate this effect, and revealed changes that occur in these neurons, including denser growths of connections between brain cells in response to the stimulation. They then traced these neurons’ connections, finding that a connection to the insular cortex is necessary for the antidepressant effect.
The functions of the insular cortex, or ‘insula’, are complex and not completely understood; but they include processing bodily sensations – such as hunger and pain – and integrating them with emotion-related signals.
“The insula hasn’t been covered much in TMS research, in part because it is too deep in the brain to reach with ordinary TMS protocols, but it is one of the most consistently altered brain regions in studies of patients with depression,” Dr. Liston said.
Experiments in mice don’t always translate to humans. So, the researchers used functional magnetic resonance imaging to map brain connections and electroencephalography to measure neuronal responses in consented patients receiving TMS. They found that TMS stimulation of the prefrontal cortex does have a downstream effect on the insula in these patients.
The results overall suggest that aiTBS’s antidepressant effect might be improved by maximising its downstream stimulation of the insula – a prospect that Dr Liston and his colleagues now plan to investigate further using their mouse model and in future clinical trials.
The identification of the neurons that are important for aiTBS’s effects and the changes that occur in them could also lead to new drug therapies targeting those neurons, Dr Liston said.
“In the meantime, another exciting strategy with great potential is to pair drug treatment with TMS to accelerate the antidepressant response,” he said.
People who wore a cooling cap for 30 minutes experienced multiple changes that could affect their mental health, according to a pilot study by Penn State researchers
Co-authors Owen Griffith, standing, and Maddie McLaughlin demonstrate the head cooling cap used in the study. Credit: Jaydyn Isiminger / Penn State. Creative Commons
Wearing a cooling cap for 30 minutes may improve a person’s sense of well-being, according to a new study by Penn State researchers.
In a recent publication in Acta Psychologica, the researchers demonstrated that head cooling may reduce depressive symptoms and alter the types of brain waves people produce. While no medical recommendations can be derived from this small, exploratory study, the results indicate head cooling may provide mental health benefits for the general population.
The work was inspired by lead author and Penn State Professor of Kinesiology Semyon Slobounov’s prior research, which found that athletes with concussions heal faster and experience fewer symptoms when their head is regularly cooled.
“A person’s mood is tied to their cognition and general brain function,” said Owen Griffith, assistant teaching professor of kinesiology at Penn State and co-author of the study. “In this study, results suggested that people enjoy the sensation of head cooling. This, in turn, improved their mood, which altered their brain activity.”
The researchers recruited 24 college students between the ages of 18 and 26. At the beginning of the study, all participants completed questionnaires that measured their mental health and cognitive abilities and underwent an electroencephalogram (EEG) to measure brain activity.
Following the EEG, participants spent 30 minutes sitting in a dimly lit room listening to ocean sounds. Half of participants wore a fitted cooling cap, which uses liquid circulating close to the head to maintain a temperature of 33 degrees Fahrenheit. The other participants wore nothing on their heads. Immediately after the cooling or sitting session, participants repeated the questionnaires and EEG.
Participants repeated the same sitting or cooling session without testing every day for one week. The day after the last session, participants repeated the questionnaires and EEG again. This design allowed the researchers to observe both the short- and longer-term effects of head cooling.
“The brain produces different types of waves that are associated with different levels of excitement or brain activation,” said Laura Cooney, co-author of the study who graduated from Penn State’s Schreyer Honor College in 2025 and based her undergraduate thesis on the research. “Alpha waves are associated with calmness. More specifically, they are indicative of less brain activity overall, so this finding suggests that there was an immediate calming effect of head cooling.”
People in the head cooling group displayed an increase in alpha brain waves during the EEG immediately following the first cooling session. They experienced a 4% increase in alpha waves while participants whose heads were not cooled displayed a .5% decrease in alpha waves.
In contrast, there was no significant difference in the alpha wave levels of the sitting and cooling groups when measured on the day after the final cooling session, suggesting cooling does not have a longer-term impact on brain wave activity, the researchers said.
Over the course of the week, both groups of participants reported a decrease in depression symptoms, but individuals in the head cooling group reported a larger decrease than those in the sitting group.
“The reduction of depression symptoms among healthy people suggests that this might be a promising treatment,” Griffith said.
The researchers said they had hypothesised head cooling affected people through changes in neural electrical activity, but the EEGs did not show evidence of that. Now, the researchers suspect the effects are psychosomatic, meaning that mental and emotional factors, rather than physiological changes, are causing people’s reduced depression symptoms and increased alpha brain wave activity.
“Anecdotally, most people who come into the lab agree that head cooling is relaxing and enjoyable,” Griffith said. “This may not be surprising. A cold compress or a bag of ice have been home treatments for migraines for many years.”
Overall, the study suggests that widespread head cooling could be useful, the researchers said.
“Head cooling shows some potential as an acute calming therapy,” Cooney said. “Not as a replacement for any current therapy, but as another tool in the toolbox.”
Slobounov, senior author of the study, agreed.
“Our previous research demonstrated that head cooling is useful for athletes recovering from concussions,” Slobounov said. “This research suggests it may be more useful to a wide group of people. It is low risk, does not involve any drugs or chemicals, and people enjoy it.”
Other Penn State researchers who contributed to this work include Zach Napora, graduate student in kinesiology and first author of the publication, Maddie McLaughlin, graduate student in kinesiology, and Elle McNally, 2025 graduate in biobehavioral health and current physician assistant graduate student.
Pilot trial reports reduced eating disorder and depressive symptoms in difficult-to-treat psychiatric condition
Photo from Freepik.
A pilot study published today in Communications Medicine demonstrates the potential of a new approach to treating anorexia nervosa, a disorder for which effective treatments have been significantly limited. The research from UC San Diego School of Medicine reports that a ketogenic nutritional intervention – a high-fat, low-carbohydrate, moderate-protein diet – was feasible and safe for patients with weight-normalised and mildly underweight anorexia nervosa. The ketogenic intervention was well-tolerated by participants, with high adherence rates and no significant weight loss observed throughout the program.
Furthermore, significant improvements were observed in eating disorder symptoms, with nearly 3 in 4 of study completers in the recovered range at study end, no longer meeting criteria for an anorexia nervosa diagnosis, and all completers experiencing an improvement in depression scores.
Study lead Guido Frank, MD, Professor of Psychiatry at UC San Diego School of Medicine, who has been studying and treating anorexia patients for over 25 years, launched this study to broaden treatment options for this high-risk population. “We urgently need new approaches to anorexia nervosa. Our work with ketogenic therapy looks beyond standard therapies and potentially at the underlying physiology of the disorder,” states Dr. Frank. “Growing evidence links anorexia nervosa to neurometabolic dysfunction, and we are hopeful that direct metabolic intervention can regulate neural function and address the psychological symptoms patients experience.”
The outpatient, nationwide, single-arm clinical study delivered a supervised 14-week ketogenic intervention, with 18 of the 22 enrolled participants (82%) completing the study. No significant change in weight was observed throughout the program (as measured by BMI). By the end of the study, 72% of study completers reached the recovered range of eating disorder symptoms as measured by eating disorder scales (Eating Disorder Examination Questionnaire, EDE-Q, and Eating Disorder Inventory-3, EDI-3) and all showed improvements in depression scores (as measured by the Beck Depression Inventory, BDI), with 72% within normal range.
For co-author Barbara Scolnick, MD, an internal medicine physician in Waban, Massachusetts, this study is the culmination of a decade-long personal journey. “The scientific inquiry that led to this research began in search of answers for my niece, Caroline Beckwith,” Dr. Scolnick shared. “Ketogenic therapy, a standard in epilepsy care, was the major catalyst, when combined with other interventions, that allowed Caroline to achieve remission after a 15-year struggle with anorexia nervosa. I am encouraged by these preliminary findings, which indicate that this treatment may provide a path forward for others like Caroline.”
While the authors acknowledge the clinical sensitivities of dietary interventions in this patient population, this study builds on priorpreliminaryevidence to provide proof of concept. The findings indicate that, when delivered with specialized medical supervision and trained support, ketogenic therapy holds potential for those who have failed to respond to traditional treatments.
“This study highlights the promise of dietary interventions that target normalizing underlying neurometabolic function for even the most intractable psychiatric conditions like anorexia nervosa,” said Jan Ellison Baszucki, co-founder and president of Baszucki Group, who funded the study. “We hope this work drives awareness and support for researching and delivering ketogenic therapy for eating disorders, providing new hope for patients and their families.”
A current extension of this study, for patients with both anorexia nervosa and bulimia nervosa diagnoses, is underway and recruiting participants nationally. Those interested in learning more or joining the study can find more information at the study site.
Bans on teenagers’ social media use are gathering pace worldwide. Their proponents claim that social media bans will improve young people’s mental health, but what evidence supports these claims? In their new Frontiers in Developmental Psychology article, Dr Monika Neff Lind and her co-authors argue that there is no solid scientific evidence behind these bans, and reason to believe they could backfire. In this guest editorial, Neff Lind explains why she and her colleagues doubt that social media bans will work, and how bans should be evaluated to determine whether they have any positive effects.
By Monika Neff Lind, PhD
In December 2025, Australia banned young people under 16 from having social media accounts. France, Greece, Spain, Denmark, Malaysia, Norway, India, Egypt, Canada, Türkiye, and the United Kingdom are hot on their heels. French president Emmanuel Macron said, “Banning social media for those under 15: this is what scientists recommend.” American senator Brian Schatz, author of the Kids Off Social Media Act, said, “Studies have revealed that when children and teens reduce or eliminate exposure to social media for longer than a month, their mental health benefits.” Proponents of youth social media bans claim that we have strong scientific evidence showing that bans will improve teenagers’ wellbeing.
As a clinical psychologist and parent, I would be thrilled if this were true, but it is not. We do not know how social media bans will affect youth because we have never studied that question. Let me explain.
Searching for evidence
When we want to test claims like ‘banning social media improves youth wellbeing’, scientific experiments are one of our most powerful tools to figure out what is causing something to happen. In experiments testing the effects of social media restriction on wellbeing, we randomly assign people to at least two groups: one quits using social media for a period of time and the other is the control or comparison group, which continues to use social media as usual. Given the strength of ban proponents’ claims, my co-authors and I were curious to know how strong the experimental evidence supporting their position was. In our new study, we collected and reviewed all of the experiments that have tested whether social media restriction improves wellbeing, and we were shocked by what we found.
Not a single social media restriction experiment has included people under the age of 16. We do not know how social media bans will affect the young people being targeted by them because we have never tested this with them!
To be fair, sometimes strong evidence in adults warrants making the leap to apply the same conclusions to teenagers. But even that leap is not justified here. The experiments with adults show weak, null, and mixed effects, with 40% of experimental studies showing harmful effects (eg, decreased life satisfaction and increased loneliness) or no effects of social media restriction. So even when adults are told repeatedly that social media is bad for their mental health and that giving it up will help, we find, on average, few to no benefits.
There is also good reason to believe that bans may backfire. First, enforcing a youth social media ban raises major ethical concerns. Enforcement efforts invade people’s privacy and are likely to hurt marginalized people more. For example, the technology that determines age based on selfie uploads makes more mistakes with young faces and people of color. Banned youth may also miss out on important resources and communications provided via social media, as schools, clubs, and most other youth-serving organizations use social media as a main form of communication.
What happens when enforcement efforts fail? Many young people will circumvent bans by creating fraudulent ‘adult’ accounts or lurking anonymously. They will retain access to social media without any of the benefits of parental controls or content filters enabled by youth accounts. The vast majority of young people oppose youth social media bans, and teens are well known for their defiance of top-down edicts that disregard their needs. Expect more conflict between teens and caregivers, not less.
To recap, we don’t know how social media bans will affect teens, and the bans may backfire. Yet the bans are still happening! Like other policies that consume resources, political capital, and time, it is imperative for governments to evaluate these actions by funding comprehensive assessments of the bans’ impacts.
What next?
The first step in measuring the impact of these bans is to determine if the bans actually change teenagers’ social media habits. Three months in, Australian authorities reported that close to 70% of social media accounts owned by people under 16 remained active.
Second, we need a careful and well-resourced plan to measure both positive well-being and mental health problems from multiple sources, including self-report, caregiver report, and objective behavioral data, to get a full picture of whether and how altered social media use affects youth.
Third, we need creative approaches to capture the real-world impacts of the bans, since true experiments are not possible and effects may be at the community as well as the individual level. For example, we could randomly assign a subset of youth (eg within a certain region) to delayed enactment of the ban. Whatever approach is taken, governments must collaborate with diverse stakeholders – including young people – to rigorously and openly evaluate potential impacts. Rushed or improvised assessment will leave room for politicization and motivated reasoning.
Big Tech has become infamous for ‘moving fast and breaking things’. Policymakers rushing to enact these bans risk repeating Big Tech’s mistakes and compounding the problems the bans are trying to solve. We cannot ban our way out of a youth mental health crisis. Rather than take things away, we should make things better.
About the author
Dr Monika Neff Lind is a clinical psychologist, science communicator, and researcher in digital mental health based at the University of California Irvine. See more of her work here.
Study finds postpartum psychosis is strongly influenced by genetics and reveals links to cholesterol metabolism, immune biology, and psychiatric disorders
Researchers at the Icahn School of Medicine at Mount Sinai have uncovered a substantial genetic component to postpartum psychosis, a rare but severe psychiatric illness that occurs in the days to weeks after childbirth. The findings, published May 14 in Molecular Psychiatry, provide new evidence that the condition has a substantial biological and genetic basis and may help guide future research into prediction, prevention, and treatment.
The study, which combined whole genome sequencing with population-level family data, identified rare damaging mutations in the gene HMGCR as associated with increased risk for postpartum psychosis. The researchers also found significant genetic overlap between postpartum psychosis and bipolar disorder, schizophrenia, and several autoimmune diseases, including rheumatoid arthritis, Sjögren’s syndrome, myasthenia gravis, and Crohn’s disease.
Postpartum psychosis affects approximately 1 in 1000 mothers and is considered a psychiatric emergency because of the elevated risk of suicide and infanticide. Symptoms can include delusions, hallucinations, severe mood changes, confusion, and disorganised behaviour.
“Our findings show that postpartum psychosis is a biological illness with a substantial genetic basis,” said Behrang Mahjani, PhD, Assistant Professor in the Departments of Psychiatry, Genetics and Genomic Sciences and Artificial Intelligence and Human Health at the Icahn School of Medicine and senior author of the paper. “It is not a parenting failure or a personal weakness, and women affected by it deserve the same medical seriousness afforded to other severe illnesses.”
This condition has historically been understudied, particularly at the genetic level, and we hope these results help move the field toward a more mechanistic understanding of why some women become vulnerable during the postpartum period.”
The study estimated that approximately 55 percent of risk for postpartum psychosis is attributable to inherited genetic factors based on family data, while whole genome sequencing analyses estimated heritability from common genetic variants at approximately 46 percent.
Researchers were particularly surprised by the identification of HMGCR, which encodes the rate-limiting enzyme in cholesterol biosynthesis. The study also revealed broader-than-expected overlap between postpartum psychosis and immune-related conditions. Researchers say the findings are consistent with longstanding clinical observations that autoimmune disease activity often changes during the postpartum period and suggest that immune biology may play a role in the illness.
“Cholesterol biosynthesis was not a pathway we had anticipated, but once HMGCR emerged, the biology became highly coherent in light of the changing dynamics of cholesterol during and after pregnancy, because cholesterol serves as the precursor for steroid hormone synthesis and prior reports linking low serum cholesterol to first episode psychosis and suicidal behaviour,” said Dr Mahjani. “The postpartum period is marked by dramatic hormonal and metabolic shifts, and this gene sits directly within pathways affected during that transition.”
The research, with analyses performed by Seulgi Jung, PhD, a postdoctoral fellow in the Mahjani Lab at Mount Sinai, is the first study to apply whole genome sequencing to postpartum psychosis, allowing investigators to examine rare damaging mutations across the genome rather than focusing solely on common genetic risk variants. The team combined data from Swedish national health registers with genomic information from the National Institutes of Health’s All of Us Research Program, enabling researchers to study one of psychiatry’s rarest and least understood conditions at an unprecedented scale.
“It is important to understand that multiple genes are involved in postpartum psychosis and that HMGCR can be used as a research tool for further scientific discovery,” said Veerle Bergink, MD, PhD, Director of the Women’s Mental Health Research Center at Mount Sinai and an author of the paper.
Future work will focus on expanding sample sizes and improving ancestral diversity. The team is now pursuing functional studies of HMGCR and other candidate genes in neuronal and immune cell models relevant to pregnancy and the postpartum period. Researchers also plan to integrate genetic findings with hormonal and immunological changes associated with childbirth to better understand why the illness emerges during such a tightly defined window.
“In the long term, our goal is to understand postpartum psychosis well enough to predict it, prevent it where possible, and develop treatments that target the underlying biology rather than symptoms alone,” said Dr Bergink.
The investigators also emphasized the importance of large-scale collaborative research infrastructure in enabling discoveries for rare conditions.
“This work would not have been possible without the NIH’s All of Us Research Program and the participants who contributed their data,” said Dr. Mahjani. “For rare and historically neglected illnesses such as postpartum psychosis, equitable access to large genomic datasets is essential for scientific progress.”
According to recent data from the Global Bipolar Cohort, only 29% of people with bipolar disorder are prescribed lithium. Despite being the “gold standard” for treating this mental health condition, we often prioritise perceptions over scientific reality, and neglect the best available treatment.
Lithium is not some complex molecule synthesised in a state-of-the-art laboratory. It is just an element, the third in the periodic table, and ever since the Australian psychiatrist John Cade discovered its therapeutic properties in 1949, it has maintained a relevance that no other psychotropic drug has been able to match.
This longevity is not a relic of the past, but a reflection of its clinical robustness. Despite decades of research and the constant emergence of new drugs, no alternative has shown comparable efficacy in the long-term prevention of manic and depressive episodes in bipolar disorder.
According to a review published in 2024, lithium is still “the mainstay treatment of mood disorders in general and in bipolar disorder specifically”. It is also the benchmark against which all other treatment options are compared, both for stabilising mood and reducing the risk of relapse.
It is the only mood stabiliser with proven efficacy in treating mania and depression, as well as in preventing relapses. Furthermore, recent studies confirm that it may also have neuroprotective properties, from the modulation of cellular pathways involved in neural plasticity to potential effects in preventing mild cognitive impairment and dementia.
These characteristics explain why international guidelines still rank it as the first-line treatment for bipolar disorder. A consensus published in 2025 stated that it should be prescribed more frequently, contrary to the unfounded reservations that still persist in clinical practice.
Suicide reduction
Above all, there is one aspect that sets lithium apart from other psychopharmaceutical drugs: its ability to reduce the risk of suicide. No other medication has demonstrated such a consistently protective effect.
A 2024 review highlighted that, despite the methodological difficulties in studying this statistically rare event, the body of evidence from clinical trials, observational studies and meta-analyses all points in the same direction: lithium reduces mortality and suicide attempts.
This is likely due to its ability to reduce impulsivity, stabilise extreme mood swings and prevent depressive relapses, all of which create the moments of greatest risk.
Beyond episodic treatment
Current research is also looking into lithium’s ability to alter the course of bipolar disorder. Not only does it stop episodes, but it also protects the brain, and evidence suggests that, unlike some antipsychotics, it improves brain connectivity and preserves verbal fluency.
In fact, there is very interesting data suggesting that it could reduce the risk of dementia by up to 50%. Even residual levels in drinking water appear to have a protective effect at a population level. Lithium is, in short, a molecule with exceptional neuroprotective potential.
But the neuroprotective effects do not stop there. Recent studies also suggest that lithium stimulates the production of brain-derived neurotrophic factor, a protein essential for neuronal survival and growth that is often reduced in patients with bipolar disorder.
In other words, it doesn’t just prevent the brain from deteriorating – it actively helps it to heal.
Blood monitoring and ‘precision medicine’
It is often argued that the need for blood tests to monitor lithium levels (the optimal therapeutic range is 0.6-0.8 millimoles per litre) is an inconvenience. However, from a rigorous clinical perspective, this monitoring is a safeguard, not a risk. It is what allows the dose to be adjusted to the exact biology of each patient, a form of “precision medicine” that we were already practising long before the term became fashionable.
We should also remember that many commonly used medicines – from anticoagulants to immunosuppressants – require the same kind of laboratory monitoring, yet they are not considered dangerous for that reason.
What lithium management requires is not fear, but rigour. So why is it prescribed less often? The answer is complex. It is partly due to pressure from the pharmaceutical industry to promote new, patentable molecules – lithium, being a natural element, cannot be patented. There is also a degree of clinical reluctance due to its narrow therapeutic window – it needs to be carefully controlled to ensure a safe yet effective dose.
However, international guidelines are clear: lithium should be the first choice. We cannot overlook it in favour of less effective alternatives simply because they appear more modern. This kind of mistake should not influence clinical practice.
Newer is not always better
Good psychopharmacology is not a question of chasing the latest developments, but of using the most appropriate treatment for each individual at every stage of their illness.
Lithium has a proven track record that spans decades, across areas that no other mood stabiliser can address simultaneously. It controls manic and depressive episodes, prevents suicide, and provides active neuroprotection. Three areas, in one single drug.
This does not mean it is right for absolutely everyone. Good psychopharmacology should always push back against fads and dogma alike, but discarding lithium’s use without ever seriously considering it deprives patients of an option that is, according to the evidence, categorically the best therapeutic option.
Our challenge today is not to reinvent the wheel, but to understand how best to use the therapeutic tools we already have. A drug doesn’t become outdated just because time has passed; it becomes outdated when new evidence emerges and supersedes it. In the case of lithium, new evidence only confirms its value.
Disproportionately high number of cases among Gen Z, Millennials, and males
Photo by Andrew Neel on Unsplash
A chemical widely used in food preservation is implicated in an uptick in recent UK deaths by suicide, with a disproportionately high number of cases among young people and boys/men, finds a comprehensive analysis of available data for the period 2019-24, published in the open access journal BMJ Public Health.
There’s now an urgent public health need to review unrestricted access to this source, to avoid further preventable deaths, say the researchers.
Rates of death by suicide have been falling across the UK since the early 1990s. But there is some evidence of a recent uptick in the numbers, coinciding with increasing reports of suicide associated with sodium nitrite poisoning around the world, they explain.
To find out if this form of poisoning is implicated in deaths by suicide in the UK, the researchers retrospectively analysed the details of cases submitted by coroners, forensic pathologists, and police forces between March 2019 and August 2024 to the primary UK laboratory that assesses nitrite and its oxidised metabolite, nitrate, in postmortem samples.
During this period, the laboratory received 274 samples from 201 cases of suspected deliberate or unintentional poisoning from across the UK, Ireland, and Gibraltar.
Most of these cases came from Greater London, South East England, Ireland, and the Midlands, although these figures may reflect coroner awareness rather than true incidence, caution the researchers.
The number of cases rose substantially after 2019, the first year samples were received for nitrite/nitrate assessment.
The final analysis included only the data for which coroners granted permission for use – 82% (164) of the cases received between 2019 and 2024.
The average age of these cases was 28, but ranged from 14–74 for males and 17–82 for females. Nearly three quarters (71%) of all the cases were among younger generations: Gen Z (33%; born 1981-96); and Millennials (38%; born 1997-2012, but listed up to 2005 to account for a separate category of minors, as 4% of cases were among those under the age of 18).
Overall, there were more men (109) than women (52) among the cases. And more than half of the cases in each generation were men, except for the oldest classified generation (Silent, born 1928-45), where the only case was that of a woman.
Levels of nitrite and nitrate found in the blood samples were 100 times higher than would be expected physiologically in 87% of cases, suggesting that swallowing the chemical was intentional, say the researchers.
The researchers highlight some caveats to their findings, including that because nitrite and nitrate analysis isn’t routinely mandated for all suspected suicides, it’s not clear exactly how many such deaths are caused by this chemical.
“It is therefore likely that the cases included here represent a substantial underestimate of the actual incidence. Secondly, the interval between death and sample receipt varied considerably, introducing the possibility that delays may have affected the accuracy of the biochemical measurements,” they say.
Nevertheless, the observed rise in cases among predominantly young people, who tend to be tech savvy, is concerning, they suggest.
“Intentional poisoning has contributed to these recent increases, and at least in the USA, this rise has been partly attributed to the use (and availability) of sodium nitrite,” they point out.
“This trend has emerged alongside freely accessible online information detailing how sodium nitrite can be obtained and used, disseminated both under the guise of providing mental health support and for more explicitly harmful purposes,” they explain.
Their findings warrant urgent action, they suggest. “Collectively, these findings establish unequivocally that use of sodium nitrite in the UK as a method of suicide is both substantial and concerning,” they write.
“Our data provide strong support for the suggestion that the improved digital literacy of younger people enables access to illicit online material promoting suicide practices and lends further support for calls for tighter legislation to prevent availability of such information in online forums,” they add.
In the meantime, steps to mitigate the effects of this type of poisoning, such as the provision of an antidote (methylthioninium chloride kits) in ambulances would be “a simple and cost effective timely method to prevent the devastating consequences of ingestion,” they point out.
*Lead researcher, Professor Amrita Ahluwalia, comments: “This is an extremely difficult subject to talk about, and we appreciate the impact that this might have on all those affected by suicide.
“What our research shows is deeply upsetting. But it makes clear why urgent steps are needed to regulate access to this chemical and to reduce the spread of harmful information about it online.”
For anyone struggling, in South Africa SADAG’s 24 hour hotline can be contacted on 0800 567 567. In the UK and Ireland, Samaritans can be contacted on tel 116 123. In the US, call or text the National Suicide Prevention Lifeline on 988, chat on 988lifeline.org, or text HOME to 741741 to connect with a crisis counsellor. In Australia, the crisis support service Lifeline is 13 11 14. Other international helplines can be found at www.befrienders.org
