Radically different
There are several kinds of medication than can help kids with Tourette’s or another tic disorder. But it’s important to note that not all kids who develop tics need treatment. Tics are very common. They often go away on their own, and they tend to bother parents more than they do the children experiencing them. Drawing attention to them can make them worse. So doing nothing can be the best strategy — at least initially.
Treatment comes into play if tics are upsetting your child, giving them pain, or making it hard for them to function in everyday life — say they’re disrupting class or getting bullied because of their tics.
The first recommended step in treatment is a specialized form of therapy called comprehensive behavioral intervention for tics (CBIT). CBIT is centered on habit reversal training, in which the child learns to recognize when they have an urge to tic and substitute a competing response — an easier, more comfortable, or less noticeable action or behavior that makes the tic impossible. For instance, if a child’s tic is jerking their head to the side, the strategy might be to put their chin down instead.
But if therapy isn’t effective in reducing a child’s tics, medication can help.
First-line medications for Tourette’s and other tic disorders are a class of drugs called alpha-2 agonists, explains Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. Alpha agonists decrease the release of a neurotransmitter called norepinephrine, which stimulates the nervous system. Alpha agonists serve as a kind of dimmer switch — by calming down the system, they make the urge to tic less frequent, less intense, and by extension, easier to control.
The two alpha-2 agonists usually prescribed for tics are guanfacine and clonidine. Dr. Mitrani reports that he usually starts by prescribing guanfacine because it comes in a longer-acting form (Intuniv), which reduces symptoms for a full 24 hours. Clonidine’s long-acting form (Kapvay) is effective for 12 hours.
Dr. Mitrani adds that there is a new liquid form of clonidine called Onyda XR that lasts 24 hours, but there isn’t yet a strong body of evidence regarding its effectiveness for tics. Onyda XR is FDA-approved for ADHD, as are Kapvay and Intuniv.
While no alpha agonist medications are FDA-approved specifically for tics, Kapvay and Intuniv are frequently used off-label for them. There is ample research on their effectiveness for tics, and they are recommended by clinical practice guidelines.
Some children respond better to several doses of short-acting guanfacine or clonidine, Dr. Mitrani notes, rather than a smoother dose of a long-acting medication. This may be because medication can be timed to peak at times when kids need tic suppression most, such as at school.
Alpha agonists are the preferred first line medications for tic disorders because their side-effects, including drowsiness and low blood pressure, are relatively mild.
If alpha agonists aren’t helping, the next step would be to try an antipsychotic medication, which can be more effective for treating tics, Dr. Mitrani notes, but their side effects are potentially more difficult to tolerate.
Aripiprazole (Abilify), which is FDA-approved for tics, is often Dr. Mitrani’s first choice among the antipsychotic medications. Abilify is a second-generation, or atypical, antipsychotic, a group of medications that have fewer side effects than older antipsychotics. Side effects of Abilify can include restlessness, agitation and weight gain.
Haloperidol (Haldol) is also effective for tics, but it’s an older antipsychotic with more side effect concerns, Dr. Mitrani notes. “I’ve only had one patient ever on Haldol, and he tolerated it well and it really helped with his tics when other things did not.”
Risperidone (Risperdal) is another atypical antipsychotic that can help, but its side effects tend to be worse than Abilify. Risperidone can cause more concerning weight gain and metabolic, neurological, and hormonal changes that can be harmful. Sometimes other medications are used to manage the weight gain from antipsychotics.
More than three-quarters of kids diagnosed with a tic disorder also have another disorder. When a child has multiple disorders, a clinician will want to evaluate which is causing the child the most difficulty and prioritize treating that.
The most common co-occurring disorder with tics is ADHD. “If tics are the bigger problem, we would start with treating them,” says Dr. Mitrani. “If the ADHD is the bigger problem, which it typically is, we usually treat that first.”
In the past, it was recommended that children with tics and ADHD avoid stimulant medication, based on research that showed it made tics worse. But newer studies counter that finding, Dr. Mitrani notes, concluding that the old research was based on very high doses of amphetamine-based medications. To lower the risk of exacerbating tics, he recommends starting kids with ADHD and tics on methylphenidate-based medication.
“If your child is starting a stimulant,” he adds, “and you see worsening of tics — and it’s clearly related to when the stimulant is in their system — the best approach might be a lower dose of stimulant combined with guanfacine or clonidine.”
One advantage to that combination, he notes, is that kids with ADHD who have behavior problems can benefit from the guanfacine or clonidine being active in the mornings before the stimulant starts working and in the evenings when it’s out of their system.
When children with tics have other co-occurring disorders, such as anxiety, OCD, or depression, treating them with medication needs to be done very carefully, Dr. Mitrani says. Since children are typically not bothered by the tics themselves, it’s almost always the other disorder that is more problematic for them. And, he adds, when the other problems cause distress, it can make the tics worse.
For anxiety, OCD, and depression, the first-line medication treatment is an antidepressant. Antidepressants can actually help alleviate tics indirectly, since they reduce anxiety. “Stress increases tics, so if there is significant anxiety and you treat the anxiety, the tics may get better,” Dr. Mitrani says. “And then maybe you don’t need the guanfacine or clonidine. But again, it depends on what the co-occurring disorders are and what’s the bigger problem for the child.”
Due to the waxing and waning nature of tics, it can be challenging to see the full effect of medication and other interventions. It is important to give medication enough time to work, Dr. Mitrani notes, typically a few weeks, to see if the overall pattern, frequency, and severity of tics has improved. And children who are being treated should continue to be monitored regularly for any changes, as tics can recur or worsen, especially when a child is excited, tired, or experiencing more stress.
Most children with tics see a natural improvement or even resolution of tics as they progress through adolescence. If there seems to be a long-standing improvement, it is appropriate to consider reducing or stopping medication, especially if the child is experiencing side effects, Dr. Mitrani notes. If tics continue and are causing distress, it is important to keep treating them.
A child going off any of these medications — alpha agonists or antipsychotics — should do so gradually, by having their dose reduced over weeks or even longer, to avoid unpleasant or dangerous side effects of sudden withdrawal.
The post Medication Treatment for Tics and Tourette’s appeared first on Child Mind Institute.
A common misconception about tantrums and meltdowns is that they’re interchangeable. But while they share some similarities in their initial expression — crying, screaming, door slamming, harsh words — they’re actually quite different. Dealing with a meltdown requires a more specialized approach, especially with kids on the autism spectrum.
The two events happen for different reasons. A child throws a tantrum when they’re angry or frustrated, acting out because they feel an injustice has been done to them. They are aware of what they’re doing and still have some sense of control. And if a child’s tantrum is ignored by their parent or caregiver, it will likely subside quickly.
Meltdowns, on the other hand, happen involuntarily and seemingly out of nowhere. They also tend to become much more intense than a typical tantrum and may involve violent behavior such as head banging, hitting others, and damaging property. Once a meltdown has started, intervention is needed to stop it, whether it’s self-imposed (e.g., removing oneself from the trigger) or external (e.g., support from the parent or caregiver). The event can last between a few minutes and several hours.
Tantrums are common among all children, but kids with autism are more likely to experience meltdowns of varying degrees, says Conner Black, PhD, associate director of the Autism Center at the Child Mind Institute.
For a child with autism, a meltdown is triggered when they become overwhelmed, whether it’s by stress, powerful emotions, sensory input, change, or something else. Their sympathetic nervous system — the network in the body responsible for our “fight-or-flight” response — goes into overdrive and they lose control.
There are several stages to an autistic meltdown and understanding them can help you know how to respond effectively. The duration and intensity of the meltdown depend on whether intervention, including learned coping skills, can stop the child from reaching a crisis point, Dr. Black explains. “Certain skills may not work every time, and that’s really no one’s fault,” he says, but once a child reaches that crisis stage, intervention is no longer useful. He describes the course of a meltdown via the phases of the behavior escalation cycle:
Once a child has started to experience a meltdown, it’s hard to get them back to baseline. Depending on the phase, certain interventions may help while others might make things worse.
First, you want to avoid triggers, Dr. Black advises. “Autistic individuals can have a lot of difficulty talking about or even understanding what their emotions are. So, it’s typically up to the parents or caregivers to identify what things can trigger them in a certain way,” he says.
For instance, some kids with autism really thrive with routine and can become agitated when there are unexpected changes. Having a visual schedule of exactly what’s going to happen during the day can help prevent that, says Dr. Black. “If you know there’s going to be a change, you can pick a time, maybe a couple of days in advance, where you talk to them about what that difference is going to be.”
And if your child is known to have meltdowns in public spaces, says Dr. Black, think about what those outside triggers are and how to prepare ahead of time. If they tend to get upset by loud noises, for example, a pair of headphones can be an item — along with phone, wallet, keys! — that you never leave the house without. If possible, work with a mental health professional to identify triggers and develop an escalation plan.
If your child has reached the agitation phase, says Dr. Black, you can try to intervene with coping skills that you’ve learned in therapy, whether it’s something as simple as removing a trigger or giving them a preferred activity in that moment to help prevent their behaviors from escalating.
Sometimes kids encounter an environment, like school, that is beyond your control but contains a wide range of potential triggers and pushes them into the agitation phase. Because their house is a more comfortable environment, kids with autism may keep themselves together at school and then quickly melt down once they get home.
“In that case, for that first hour, let them have their alone time where they can just chill,” Dr. Black suggests. “It could be eating snacks, watching a TV show, or even just sitting quietly in their room. Maybe it’s engaging in some sort of self-stimming behavior.” This can give them the space to cool down and take some time away from any sort of outside stimuli that could push them to move from the agitation phase into the escalation point of a meltdown.
It can be hard to anticipate every possible trigger, especially when there might be multiple at once on any given day. And sometimes coping strategies aren’t enough to keep a child from escalating or the trigger is too strong. Still, there are some things that Dr. Black suggests you can do to try to keep them from reaching that crisis point.
Too much talking can be overwhelming for the child at this stage and might push them to crisis, Dr. Black explains, so the less communication the better. “A simple instruction looks like using just a short sentence. Say there’s a loud noise, for example. You can just say, ‘Go get your headphones,’” he says.
Instead of trying to communicate verbally, you can hold up a visual prompt. “If your child has already been working with a therapist or if they’ve learned some coping skills, it would be helpful to have a laminated sheet readily available with their name and pictures of four different coping skill options — like headphones, deep breathing, coloring, sitting alone in their room.”
Dr. Black advises only giving a few options, as it’s already difficult for the child to focus while they’re upset. Additionally, if they don’t choose one right away and you want to try again, he recommends that you “let there be silence for 60 seconds at minimum between prompts, because you don’t want to over-prompt and exacerbate the situation even more.” But providing these choices allows them to maintain their autonomy, which is important during escalation.
“Once they get to that apex, they’ve reached the point of no return and just need to go through the process,” says Dr. Black. He stresses that at this point, communication needs to be very minimal or nonexistent.
“The goal switches to really being able to maintain safety for both the individual as well as the family members in the area,” Dr. Black explains. “If they’re harming themselves, such as head banging, move them to their bed so at least it’s on something that’s softer and not going to potentially cause significant injury.”
Efforts to make sure the child is as safe as possible can put you in harm’s way. “If there’s aggression, you can be watching and making sure they’re safe but not getting too close where you could get aggressed upon,” says Dr. Black.
If there are other children in the house, Dr. Black advises that you make plans for how to keep them safe. “Maybe they can go to their room and lock the door while it’s happening,” he says. “Some families have the other kids go to the car and sit and wait until their parents come out to get them.”
If the crisis phase goes on for a long period of time, says Dr. Black, “this is when you’d have to think about calling 911. And as kids become adolescents, the response is going to look a lot different. Because of size alone, it’s a little bit easier to manage the situation in a 5-year-old than it would be in a 15-year-old.”
Dr. Black advises that you get in touch with your local police department or EMT service in advance to let them know you have a child with autism in the home, so if you call during an emergency, they are already familiar with your family.
Watch for signs that the child is beginning to de-escalate, Dr. Black says. “All you’re doing at this point is maintaining safety until you’re really able to see a lessening of the intensity of the behavior or the frequency decreases a little bit.” Then, he says, you can start to slowly communicate with them again. You really need to be careful here, because it may look like they’re calming down, but if they’re pushed too hard and they’re not ready to talk, they might go right back into crisis phase.
At the recovery phase, “the whole family is recovering,” Dr. Black says. It’s at this point where you can all debrief and work through what may have triggered this escalation and how to possibly prevent it in the future.
“Make sure you’re also debriefing separately with the other siblings in the home after it happens,” Dr. Black adds. “They’ve just witnessed something that may have been traumatic and really stressful for them. There’s often so much focus given to the child with the big behaviors in the moment.”
Sometimes, a child or teen may suffer from frequent meltdowns to the point that it’s interfering with their quality of life and their ability to attend school. At that time, a mental health professional may recommend working with a psychiatrist to add medication to their treatment.
The type of medication depends on the underlying mechanisms contributing to the behaviors, Dr. Black says. “For instance, if it’s coming from significant anxiety, psychiatrists may prescribe an SSRI like Prozac or Zoloft. If a child has co-occurring ADHD, which is very common, stimulant or non-stimulant ADHD medication might be recommended. And if the behavior stems from irritability or some kind of rigidity, antipsychotic medications like Abilify or risperidone can be useful.”
Dr. Black notes that when kids receive the support they need, their quality of life really improves. “I’ve seen that when families work with therapists to come up with different behavioral plans and figure out a proper medication regimen, there’s a lot of improvement in behavior challenges,” he says. “The duration, frequency, and intensity of the meltdowns decrease as the child learns how to handle strong emotions and parents learn how to respond to them. And the medication can help to increase their likelihood of being able to use coping skills or regulation techniques to calm back down when they start to get really frustrated.”
The post How to De-Escalate an Autistic Meltdown appeared first on Child Mind Institute.
Circa 1970, the renowned Russian neuropsychologist Alexander Luria together with Karl Pribram from Stanford University and other neuroscientists of that era introduced the term “executive functions” into the scientific lexicon to denote complex behaviors such as attention and awareness. They identified the frontal lobe — the front of the brain — as the “executive of the brain” responsible for these behaviors based on their experiments with primates and patients with specific brain injuries.
Over time, the concept evolved to include mental processes needed to focus, concentrate, and pay attention when challenged by multiple simultaneous sources of information to weigh options and make informed decisions as opposed to impulsive ones.
Thousands of genes are expressed differently in the brains of men and women, researchers have discovered.
The findings could help explain differences in neurodevelopmental, psychiatric, and neurodegenerative disorders between the sexes.
While men are more likely to experience schizophrenia, attention deficit hyperactivity disorder, and Parkinson’s disease, women are more prone to mood disorders and Alzheimer’s disease.
The U.S. study, in Science, is the first systemic single-cell survey of sex differences in gene expression across multiple regions of the human brain.
“Together, these findings provide a comprehensive map of molecular sex differences in the human brain and offer initial insight into their underlying mechanisms and potential functional consequences,” Alex DeCasien, PhD, from the National Institute of Mental Health in Bethesda, Maryland, told Inside Precision Medicine.
DeCasien and co-workers conducted a high-resolution analysis of gene expression in tissue samples from the brains of 15 men and 15 women using single-nucleus RNA sequencing.
They then used data from earlier large neuroimaging studies to select six cortical regions to sample, four of which showed sex-related differences in grey matter volume and two in which no such differences were found.
The team found subtle but widespread differences in gene activity between men and women. Biological sex explained very little of the variance in gene expression across the brain, at less than 1%, but differences were widespread—with more than 3000 genes showing different expression according to sex in at least one cortical region.
The greatest sex-related differences in gene expression were on the sex chromosomes. However, most of the genes showing sex-related variations in expression were autosomal—carried on one of the 22 numbered non-sex chromosomes.
The predominant driver for sex-biased expression of genes on these autosomal chromosomes were sex steroid hormones such as estrogen and testosterone.
Surprisingly, more than half the X chromosome genes in women were expressed in both alleles for at least one cell type. This indicated that many had escaped X chromosome inactivation—a female phenomenon in which one of the two X chromosomes is switched off early in development to stop women producing double the number of X-linked gene products to men.
“That finding has implications for understanding sex-biased disease susceptibility because several genes implicated in neurodevelopmental disorders reside on the X chromosome,” commented Jessica Tollkuhn, PhD, from Cold Spring Harbor Laboratory, and S Marc Breedlove, from Michigan State University, in an accompanying Perspective article.
They noted that autosomal genes showing sex-biased expression were substantially enriched for extracellular matrix components, hormone signaling pathways, and metabolic processes. “Genes with greater expression in women were enriched for mitochondrial and synaptic functions, whereas male-biased genes were associated with metabolic and structural pathways,” the editorialists added.
“By pinpointing these sexually differentiated processes, the data provide a treasure trove for the discovery of biomarkers of and/or therapeutic targets for differential disease risk in men and women.”
DeCasien and team added: “These findings raise the possibility that sex differences in gene expression modulate the magnitude of genetic effects at risk loci, contributing to differences in disease vulnerability and to reduced portability of polygenic risk prediction across sexes.”
The post Brain Gene Variations Help Explain Neurological and Psychiatric Sex Differences appeared first on Inside Precision Medicine.
You’ve probably heard some version of this idea before: that many of us have an “inner Neanderthal.” That is to say, around 45,000 years ago, when Homo sapiens first arrived in Europe, they met members of a cousin species—the broad-browed, heavier-set Neanderthals—and, well, one thing led to another, which is why some people now carry a small amount of Neanderthal DNA.
This DNA is arguably the 21st century’s most celebrated discovery in human evolution. It has been connected to all kinds of traits and health conditions, and it helped win the Swedish geneticist Svante Pääbo a Nobel Prize.
But in 2024, a pair of French population geneticists called into question the foundation of the popular and pervasive theory.
Lounès Chikhi and Rémi Tournebize, then colleagues at the Université de Toulouse, proposed an alternative explanation for the very same genomic patterns. The problem, they said, was that the original evidence for the inner Neanderthal was based on a statistical assumption: that humans, Neanderthals, and their ancestors all mated randomly in huge, continent-size populations. That meant a person in South Africa was just as likely to reproduce with a person in West Africa or East Africa as with someone from their own community.
Archaeological, genetic, and fossil evidence all shows, though, that Homo sapiens evolved in Africa in smaller groups, cut off from one another by deserts, mountains, and cultural divides. People sometimes crossed those barriers, but more often they partnered up within them.
In the terminology of the field, this dynamic is called population structure. Because of structure, genes do not spread evenly through a population but can concentrate in some places and be totally absent from others. The human gene pool is not so much an Olympic-size swimming pool as a complex network of tidal pools whose connectivity ebbs and flows over time.
This dynamic greatly complicates the math at the heart of evolutionary biology, which long relied on assumptions like randomly mating populations to extract general principles from limited data. If you take structure into account, Chikhi told me recently, then there are other ways to explain the DNA that some living people share with Neanderthals—ways that don’t require any interspecies sex at all.
“I believe most species are spatially organized and structured in different, complex ways,” says Chikhi, who has researched population structure for more than two decades and has also studied lemurs, orangutans, and island birds. “It’s a general failure of our field that we do not compare our results in a clear way with alternative scenarios.” (Pääbo did not respond to multiple requests for comment.)
The inner Neanderthal became a story we could tell ourselves about our flaws and genetic destiny: Don’t blame me; blame the prognathic caveman hiding in my cells.
Chikhi and Tournebize’s argument is about population structure, yes, but at heart, it is actually one about methods—how modern evolutionary science deploys computer models and statistical techniques to make sense of mountains upon mountains of genetic data.
They’re not the only scientists who are worried. “People think we really understand how genomes evolve and can write sophisticated algorithms for saying what happened,” says William Amos, a University of Cambridge population geneticist who has been critical of the “inner Neanderthal” theory. But, he adds, those models are “based on simple assumptions that are often wrong.”
And if they’re wrong, what’s at stake is far more than a single evolutionary mystery.
Back in 2010, Pääbo’s lab pulled off something of a miracle. The researchers were able to extract DNA from nuclei in the cells of 40,000-year-old Neanderthal bones. DNA breaks down quickly after death, but the group got enough of it from three different individuals to produce a draft sequence of the entire Neanderthal genome, with 4 billion base pairs.
As part of their study, they performed a statistical test comparing their Neanderthal genome with the genomes of five present-day people from different parts of the world. That’s how they discovered that modern humans of non-African ancestry had a small amount of DNA in common with Neanderthals, a species that diverged from the Homo sapiens line more than 400,000 years ago, that they did not share with either modern humans of African ancestry or our closest living relative, the chimpanzee.
Pääbo’s team interpreted this as evidence of sexual reproduction between ancient Homo sapiens and the Neanderthals they encountered after they expanded out of Africa. “Neanderthals are not totally extinct,” Pääbo said to the BBC in 2010. “In some of us, they live on a little bit.”
The discovery was monumental on its own—but even more so because it reversed a previous consensus. More than a decade earlier, in 1997, Pääbo had sequenced a much smaller amount of Neanderthal DNA, in that case from a cell structure called a mitochondrion. It was different enough from Homo sapiens mitochondrial DNA for his team to cautiously conclude there had been “little or no interbreeding” between the two species.
After 2010, though, the idea of hybridization, also called admixture, effectively became canon. Top journals like Science and Nature published study after study on the inner Neanderthal. Some scientists have argued that Homo sapiens would never have adapted to colder habitats in Europe and Asia without an infusion of Neanderthal DNA. Other research teams used Pääbo’s techniques to find genetic traces of interbreeding with an extinct group of hominins in Asia, called the Denisovans, and a mysterious “ghost lineage” in Africa. Biologists used similar tests to find evidence of interbreeding between chimpanzees and bonobos, polar and brown bears, and all kinds of other animals.
The inner-Neanderthal hypothesis also took a turn for the personal. Various studies linked Neanderthal DNA to a head-spinning range of conditions: alcoholism, asthma, autism, ADHD, depression, diabetes, heart disease, skin cancer, and severe covid-19. Some researchers suggested that Neanderthal DNA had an impact on hair and skin color, while others assigned individuals a “NeanderScore” that was correlated with skull shape and prevalence of schizophrenia markers. Commercial genetic testing companies like 23andMe started offering customers Neanderthal ancestry reports.
The inner Neanderthal became a story we could tell ourselves about our flaws and genetic destiny: Don’t blame me; blame the prognathic caveman hiding in my cells. Or as Latif Nasser, a host of the popular-science program Radiolab, put it when he was hospitalized with Crohn’s disease, another Neanderthal-associated condition: “I just keep imagining these tiny Neanderthals … just, like, stabbing me and drawing these little droplets of blood out of me.”
“These things become meaningful to people,” Chikhi says. “What we say will be important to how people view themselves.”
When population geneticists built the theoretical framework for evolutionary biology in the early 20th century, genes were only abstract units of heredity inferred from experiments with peas and fruit flies. Population genetics developed theory far more quickly than it accumulated data. As a result, many data-driven scientists dismissed the study of evolution as a form of storytelling based on unexamined assumptions and preconceived ideas.
By the ’90s, though, genes were no longer abstractions but sequenced segments of DNA. Genomic sequencing grounded evolutionary studies in the kind of hard data that a chemist or physicist could respect.
Yet biologists could not simply read evolutionary history from genomes as though they were books. They were trying to determine which of a nearly infinite number of plausible histories was the most likely to have created the patterns they observed in a small sample of genomes. For that, they needed simplified, algorithmic models of evolution. The study of evolution shifted from storytelling to statistics, and from biology to computer science.
That suited Chikhi, who as a child was drawn to the predictable laws and numerical precision of math and science. He entered the field in the mid-’90s just as the first big studies of human DNA were settling old debates about human origins. DNA showed that Africa harbored far more genetic diversity than the entire rest of the planet. The new evidence supported the idea that modern humans evolved for hundreds of thousands of years in Africa and expanded to the other continents only in the last 100,000 years. For Chikhi, whose parents were Algerian immigrants, this discovery was a powerful challenge to the way some archaeologists and biologists talked about race. DNA could be used to deconstruct rather than encourage the pernicious idea that human races had deep-seated evolutionary differences based on their places of origin.
At the same time, though, he was wary of the tendency to treat DNA as the final verdict on open questions in evolution. Chikhi had been surprised when, back in 1997, Pääbo and his team used that small amount of mitochondrial DNA to rule out hybridization between Homo sapiens and Neanderthals. He didn’t think that the absence of Neanderthal DNA there necessarily meant it wouldn’t be found elsewhere in the Homo sapiens genome.
Chikhi’s own research in the aughts opened his eyes to the gaps between historical reality and models of evolution. For one, despite the assumption of random mating, none of the animals Chikhi studied actually mated randomly. Orangutans lived in highly fragmented habitats, which restricted their pool of potential mates, and female birds were often extremely picky about their male partners.
These factors could confound an evolutionary biologist’s traditional statistical tool kit. Scientists were starting to apply a mathematical technique to estimate historical population sizes for a species from the genome of just a single individual. This method showed sharp population declines in the histories of many different species. Chikhi realized, though, that the apparent declines could be an artifact of treating a structured population as one that evolved with random mating; in that case, the technique could indicate a bottleneck even if all the subgroups were actually growing in size. “This is completely counterintuitive,” he says.
That’s at least partly why, when Pääbo’s 2010 Neanderthal genome came out, Chikhi was impressed with the sheer technical accomplishment but also leery of the findings about hybridization. “It was the type of thing we conclude too quickly based on genetic data,” he says. Pääbo’s work mentioned population structure as a possible alternative explanation—but didn’t follow up.
Just a couple of years later, a pair of independent scientists named Anders Eriksson and Andrea Manica picked up the idea, building a model with simple population structure that explicitly excluded admixture. They simulated human evolution starting from 500,000 years ago and found that their model produced the same genomic patterns Pääbo’s group had interpreted as evidence of hybridization.
“Working with structured models is really out of the comfort zone of a lot of population geneticists,” says Eriksson, now a professor at the University of Tartu in Estonia.
Their research impressed Chikhi. “At the time, I thought people would focus on population structure in the evolution of humans,” he says. Instead, he watched as the inner-Neanderthal hypothesis took on a life of its own. Scientists produced new methods to quantify hybridization but rarely examined whether population structure would yield the same results. To Chikhi, this wasn’t science; it was storytelling, like some of the old narratives about the evolution of racial differences.
Chikhi and Tournebize decided to take a crack at the problem themselves. “I’ve always been very skeptical about science, and population genetics in particular,” says Tournebize, now a researcher at the French National Research Institute for Sustainable Development. “We make a lot of assumptions, and the models we use are very simplistic.” As detailed in a 2024 paper published in Nature Ecology & Evolution, they built a model of human evolution that replaced randomly mating continent-wide populations with many smaller populations linked by occasional migration. Then they let it run—a million times.
At the end of the simulation, they kept the 20 scenarios that produced genomes most similar to the ones in a sample of actual Homo sapiens and Neanderthals. Many of these scenarios produced long segments of DNA like the ones their peers argued could only have been inherited from Neanderthals. They showed that several statistics, which other scientists had proposed as measurements of Neanderthal DNA, couldn’t actually distinguish between hybridization and population structure. What’s more, they showed that many of the models that supported hybridization failed to accurately predict other known features of human evolution.
“A model will say there was admixture but then predict diversity that is totally incompatible with what we actually know of human diversity,” Chikhi says. “Nobody seems to care.”
So how did Neanderthal DNA wind up in living people if not via interspecies passion? Chikhi and Tournebize think it’s more likely that it was inherited by both Neanderthals and some sapiens groups in Africa from a common ancestor living at least half a million years ago. If the sapiens groups carrying those genetic variants included the people who migrated out of Africa, then the two human species would have already had the DNA in common when they came into contact in Europe and Asia—no sex required.
“The interpretation of genetic data is not straightforward,” Chikhi says. “We always have to make assumptions. Nobody takes data and magically comes up with a solution.”
Most of the half-dozen population geneticists I spoke with praised Chikhi and Tournebize’s ingenuity and appreciated the spirit of their critique. “Their paper forces us to think more critically about the model we use for inference and consider alternatives,” says Aaron Ragsdale, a population geneticist at the University of Wisconsin–Madison. His own work likewise suggests that the earliest Homo sapiens populations in Africa were probably structured—and that this is the likely reason for genomic patterns that other research groups had attributed to hybridization with a mysterious “ghost lineage” of hominins in Africa.
Yet most researchers still believe that modern humans and Neanderthals did probably have children with each other tens of thousands of years ago. Several pointed to the fact that fossil DNA of Homo sapiens who died thousands of years ago had longer chunks of apparent Neanderthal DNA than living people, which is exactly what you would expect if they had a more recent Neanderthal ancestor. (To address this possibility, Chikhi and Tournebize included DNA from 10 ancient humans in their study and found that most of them fit the structured model.) And while the Harvard population geneticist David Reich, who helped design the statistical test from Pääbo’s 2010 study, declined an interview, he did say he thought Chikhi and Tournebize’s model was “weak” and “very contrived,” adding that “there are multiple lines of evidence for Neanderthal admixture into modern humans that make the evidence for this overwhelming.” (Two other authors of that study, Richard Green and Nick Patterson, did not respond to requests for comment.)
Nevertheless, most scientists these days welcome the development of structured, or “spatially explicit,” models that account for the fact that any given member of a population is usually more closely related to individuals living nearby than to those living far away.
Loosening our attachment to certain narratives of evolution can create space for wonder at the sheer complexity of life’s history.
Other scientists also say that random mating isn’t the only assumption in population genetics that merits scrutiny. Models rarely factor in natural selection, which can also create genetic patterns that look like hybridization. Another common assumption is that everyone’s DNA mutates at the same, constant rate. “All the theory says the mutation rate is fixed,” says Amos, the Cambridge population geneticist. But he thinks that rate would have slowed drastically in the group of Homo sapiens that expanded to Europe around 45,000 years ago. This, too, could have created genomic patterns that other scientists interpret as evidence of interbreeding with Neanderthals.
The point here isn’t that a complex model of evolution with many moving pieces is necessarily better than a simple one. Scientists need to reduce complexity in order to see the underlying processes more clearly. But simple models require assumptions, and scientists need to reevaluate those assumptions in light of what they learn. “As you get more data, you can justify more complex models of the world,” says Mark Thomas, a population geneticist at University College London, who wrote a history of random mating in population genetics that highlighted how the field was starting to see it as “a limiting assumption as opposed to a simplifying one.”
It can feel discouraging to couch conversations about the past in confusing terms like “population structure” and “mutation rates.” It seems almost antithetical to the spirit of science to talk more about uncertainty at the same time we are developing powerful technologies and enormous data sets for analyzing evolution. These tools often yield novel answers, but they can also limit the questions we ask. The French archaeologist Ludovic Slimak, for example, has complained that the idea of the inner Neanderthal has domesticated our image of Neanderthals and made it difficult to imagine their humanity as distinct from our own. Investigating Neanderthal DNA is sexier to many young researchers than searching for archaeological and fossil evidence of how Neanderthals actually lived.
Loosening our attachment to certain narratives of evolution can create space for wonder at the sheer complexity of life’s history. Ultimately, that’s what Chikhi and Tournebize hope to do. After all, they don’t believe the question of population structure versus hybridization is either-or. It’s possible, and even likely, that both played a role in human evolution. “Our structured model does not necessarily mean that no admixture ever took place,” Chikhi and Tournebize wrote in their study. “What our results suggest is that, if admixture ever occurred, it is currently hard to identify using existing methods.”
Future methods might disentangle the different factors, but it’s just as important, Chikhi says, for scientists to be up-front about their assumptions and test alternatives. “There’s still so much uncertainty on so many aspects of the demographic history of Neanderthals and Homo sapiens,” he notes.
Keep that in mind the next time you read about your inner Neanderthal. The association between this DNA and some diseases may be real, of course—but would journals publish these studies without the additional claim that the DNA is from Neanderthals? Any good storyteller knows that sex sells, even in science.
Ben Crair is a science and travel writer based in Berlin.