The Sentinel Phenotype: a theoretical bioenergetic and neurobiological framework for high-fidelity predictive systems (HEPOE Theory)

The HEPOE Theory (High Entropy Predictive Organization Efficiency) proposes a novel conceptual framework for understanding Giftedness (HA/G), moving beyond academic performance-based models toward a biophysical and neuroscientific foundation. Through a theoretical synthesis grounded in the Free Energy Principle and Biological Thermodynamics, the gifted individual is redefined as a “Sentinel”: a high-fidelity sampling system specialized in the early detection of isomorphy and the reduction of systemic entropy. This framework reinterprets Charles Spearman’s general intelligence (g) as a macroscopic manifestation of hardware efficiency, where reasoning ability is proposed to be fundamentally constrained by working-memory capacity and the metabolic economy of ATP resynthesis. We hypothesize that the hardware operates under an “open sensory gating” regime and low latent inhibition, leading to high metabolic costs and chronic allostatic load. The paper introduces the original concept of Predictive Moral Injury to conceptualize the potential somatic damage resulting from the early perception of ethical-systemic collapses within low-resolution environments. The HEPOE Unification Matrix integrates decades of classical literature and proposes a rigorous differential diagnosis against the pathologization of ASD, ADHD, and PTSD. It hypothesizes that the Sentinel’s exhaustion is not a dysfunction, but a logistical byproduct of high predictive performance under entropy-saturated conditions.
<![CDATA[At the 2026 ASCP Annual Meeting, Eric Konofal, MD, PhD, argued that sleep assessment should become a routine part of ADHD evaluation and treatment.]]>

Transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration: a case report

BackgroundAdvanced Alzheimer’s disease (AD) is generally regarded as a stage of irreversible functional decline. Psilocybin is known to transiently alter large-scale brain network dynamics and to induce plasticity-related mechanisms in preclinical models, yet clinical data in advanced dementia remain lacking.Case presentationWe report the case of an octogenarian Japanese-American woman with a 10-year history of Alzheimer’s disease, including 5 years of marked hypofunction and predominantly monosyllabic speech. Baseline features included chronic urinary incontinence, executive dysfunction, dysphagia, dependent mobility, flat affect, and severe reduction in spontaneous communication. The patient received 5 g of orally administered psilocybin-containing mushrooms (Enigma strain). The acute phase was marked by autonomic activation, clinically suspected hyperthermia, profuse sweating, and a prolonged deep sleep-like state. Approximately 19 h post-administration, spontaneous autobiographical speech emerged. Over subsequent days and weeks, functional improvements included restoration of urinary continence, improved ambulation, autonomous dressing, increased emotional responsiveness, sustained social interaction, contextual memory retrieval, preserved working memory for social context, and spontaneous conversational engagement.ConclusionThis case documents transient multidomain functional improvement in advanced Alzheimer’s disease following psilocybin administration. The findings do not imply disease reversal but suggest that residual functional capacity may persist in late-stage neurodegeneration and may become transiently accessible under specific neuromodulatory conditions.
<![CDATA[APA session probes ADHD stimulant prescribing, contrasts population studies with RCTs, and explores education and brain effects.]]>

A bibliometric analysis of neuroimaging studies on cognitive control in autism spectrum disorder (2000–2025)

ObjectiveThis study aims to systematically analyze neuroimaging research on cognitive control in Autism spectrum disorder (ASD) from 2000 to 2025 using bibliometric methods, in order to reveal the evolutionary trajectory, core knowledge base, research hotspots, and future frontiers of the field.MethodsA search was conducted on the Web of Science Core Collection and Scopus databases, resulting in the inclusion of 1,581 relevant articles. VOSviewer and the Bibliometrix package in R were utilized to conduct a comprehensive visualization and quantitative analysis of annual publication volume, country/institution/author collaboration networks, keyword co-occurrence, document co-citation, and thematic evolution.Results(1) The volume of research literature showed exponential growth, with an annual growth rate of 21.61%, entering a period of rapid development particularly after 2012, which is closely related to the popularization of functional magnetic resonance imaging (fMRI) technology. (2) “Functional connectivity,” “executive function,” and “default mode network” were the most central keywords. “Functional connectivity” rapidly became a hub connecting various themes after 2010, marking a paradigm shift from “functional localization” to “brain network dysregulation.” (3) The “Triple network model” proposed by Menon was the most cited document, laying the core theoretical foundation for understanding ASD as a disorder of large-scale brain network dysfunction. (4) “Transdiagnostic” research has emerged as a new hotspot, while “multimodal imaging,” “machine learning,” and “dynamic connectivity” represent highly promising future directions.ConclusionOver the past two decades, neuroimaging research on cognitive control in ASD has undergone a profound paradigm shift: from focusing on abnormal activation in isolated brain regions to exploring the static and dynamic dysregulation of large-scale brain networks. The research perspective has also expanded from a single-disorder model to a transdiagnostic framework that includes comparisons with other neurodevelopmental disorders (e.g., ADHD). Future research should focus on the fusion of multimodal data, the application of computational psychiatry methods, and the translation of basic research findings into personalized clinical interventions.
<![CDATA[David W. Goodman, MD, discusses the new ASCP consensus recommendations on when clinicians should consider deprescribing stimulants as part of good ADHD care.]]>

Melatonin for Kids: Is It Safe?

If you’ve spent any time talking to other parents about sleep, you’ve probably heard about melatonin. One person swears by it. Someone else warns against it. And if your child is struggling to fall asleep, it can be hard to know what to believe.

Melatonin is widely available, often marketed as a “natural” sleep aid, and increasingly used to help kids of all ages. But it may not be the right solution. The key is knowing when it makes sense, when it doesn’t, and how to make it work best as part of a bigger sleep plan.

What is melatonin?

Melatonin is a hormone the body produces naturally to regulate sleep. As it gets dark, the brain releases melatonin to signal that it’s time to wind down. Light exposure at night — especially blue light from screens — can disrupt the body’s natural rhythm so you don’t feel sleepy even when it’s bedtime.

“Melatonin supplements can help facilitate that circadian rhythm, that 24-hour sleep cycle,” says Rohn Nahmias, DO, a child and adolescent psychiatrist at the Child Mind Institute. Because it’s sold over the counter, melatonin seems to be harmless. In practice, clinicians are much more cautious. While they tend to consider it relatively low risk, with few side effects, they still don’t view it as something to take casually or indefinitely.

That’s because there are real gaps in what we know about melatonin — especially when kids take it regularly over long periods. “The longest study was about four years, and they did not find any issues,” says Judith Owens, MD, MPH, a pediatric sleep expert and professor of neurology at Harvard Medical School. “But the data are very limited in subject numbers and long-term follow-up.”

So, the question parents often ask — is melatonin safe for kids? — doesn’t have a simple yes or no answer. The more useful question may be whether melatonin is right for your kid and what guidelines should you follow if you’re going to give it to them.  

That’s why it’s especially important to consult your child’s pediatrician or tell them if you’ve already started your child on melatonin. “Because melatonin is over the counter, families often forget to mention it,” says Dr. Nahmias. But doctors need to know about supplements, especially if a child is on other medications or has additional health concerns.

Melatonin can be helpful in the right situations, but using it without looking deeper can be “kind of slapping a Band-Aid onto a problem,” Dr. Nahmias says. In his practice, he always wants to rule out anxiety, mood concerns, or a medical issue that may be impacting sleep (such as snoring, breathing problems, or pain) before introducing something new like melatonin.

When melatonin can help

Melatonin is most useful when the issue is falling asleep, not staying asleep. For example, if your child has persistent trouble falling asleep — not just occasional bedtime resistance — and you have already tried using behavioral strategies.

The immediate-release melatonin sold in the United States is primarily helpful for sleep onset. (A prolonged-release form approved in the UK and EU may help with staying asleep, but it’s not available here.) Melatonin can also help with circadian rhythm issues like delayed sleep-wake phase disorder, when a child or teen’s natural sleep and wake times are much later than their schedule allows. “That is the other real indication for melatonin,” Dr. Owens says.

How to use melatonin thoughtfully

If melatonin does make sense for your child, experts agree: Start low and go slow. Dr. Nahmias recommends beginning with 1 to 2 milligrams for kids four and up and increasing the dose only if needed — up to 3 milligrams for kids ages six to 10. Many children respond well to low amounts — more than 5 milligrams, he says, isn’t much more effective and is more likely to cause side effects like grogginess or irritability. Dr. Owens emphasizes a similarly cautious approach: Use the lowest effective dose, monitor whether it’s actually helping, and reassess regularly rather than letting it quietly become an open-ended routine.

Dr. Nahmias recommends using melatonin in “clusters” — short, purposeful stretches of nightly use to help realign the circadian rhythm — and then pulling back to use as needed. A cluster might make sense for a few weeks after travel, during a tough transition, or while the family works on behavioral changes.

If a child needs melatonin every night for months, that’s a signal to dig deeper. “That tells me that there’s something likely going on underneath that’s not being addressed,” Dr. Nahmias says.

Side effects and safety

Melatonin is generally well tolerated, but knowing the possible side effects can help you catch problems early. The most common is grogginess the next morning. Others include irritability, headaches, dizziness, stomach upset, and — in toddlers and younger children — increased bedwetting. Some children may also experience vivid dreams or nightmares, though these tend to be mild.

Check in with your child’s pediatrician if side effects appear, if your child needs melatonin frequently or for more than a short period, if the dose keeps creeping up, if their sleep problems are worsening, or if you notice signs of anxiety, depression, or ADHD that might be driving their sleep struggles.

One important safety note: melatonin gummies look like candy, and Dr. Owens describes an “astronomical increase” in calls to poison control centers and emergency room visits related to melatonin in children, largely due to accidental ingestion. Store melatonin — especially gummies — like any other medication: out of reach, ideally in a locked cabinet. Never present them to children as a treat.

A bigger concern: what’s actually in the bottle

Melatonin isn’t tightly regulated in the United States, which means the dose on the label may not match what’s actually in the product. Studies have found that 22 out of 25 over-the-counter melatonin gummies were labeled inaccurately, with some containing far more melatonin than advertised.
Dr. Owens describes the variability as “huge” and says she was genuinely shocked by the findings. When shopping, look for products with a USP Verified mark. USP (United States Pharmacopeia) is an independent nonprofit that tests supplements to confirm the product contains what the label says, in the correct amount, and without harmful contaminants.

Melatonin for kids with ADHD or autism

There’s solid evidence that melatonin can benefit children with neurodevelopmental conditions, particularly autism and ADHD, who are more likely to have disrupted sleep-wake cycles. “There is a pretty robust literature supporting efficacy, without a lot of side effects,” Dr. Owens says about children on the autism spectrum.

But Dr. Nahmias encourages parents of kids with autism or ADHD to take a close look at bedtime routines before turning to melatonin. “Both of those populations of kids do best when there is structure put into their day,” he says. He recommends having a posted list of the sleep routine that a child needs to accomplish as a helpful visual reminder that will start to become second nature as it is built into their evening.

If getting to sleep is still an issue, trying melatonin makes sense. But for kids with autism and ADHD, it may take more time to see an effect. “It can be helpful to give it a bit longer to re-right the sleep cycle,” Dr. Nahmias says. “Trying it for two to three months may be more beneficial than just a few weeks.”

 Many neurodivergent kids may also need to stay on melatonin longer than neurotypical children.  “This makes it absolutely imperative that administration of melatonin for these children is under the supervision of a health professional who can monitor efficacy, side effects, and recommend periodic ‘off-drug holidays,’” Dr. Owens says. The goal is to get sleep back on track and consistent for some time. Once that goal is achieved, Dr. Nahmias adds, “it is important that there be attempts to take breaks from the medication or try lower doses.”

When melatonin is not likely to help

Melatonin is often used in situations where it’s unlikely to make much difference. That’s not a criticism of parents — sleep deprivation is exhausting, and it’s natural to reach for something that seems gentle and accessible. But if the real issue is an inconsistent routine, untreated anxiety, or an unidentified medical problem, melatonin may only be a temporary solution. The real problem will persist and need diagnosis and treatment.

For younger children — kids under five, especially — sleep problems are almost always better addressed with changes in habits and routines rather than supplements. For kids under two, “there’s no reason to use melatonin… and really, honestly, under five, for the most part,” Dr. Owens says. At those ages, behavioral approaches almost always work better.

What to try before using melatonin

Small, consistent changes in sleep habits can make a real difference — and unlike a supplement, these strategies can help children build skills that support sleep for years to come. Dr. Nahmias focuses on what’s often called sleep hygiene: a consistent bedtime and wake time, a predictable wind-down routine, and a sleep environment that actually supports rest, like keeping the bedroom dark, cool, and quiet. “The bed is meant for one thing and one thing only, and that is for sleep,” he says, emphasizing no TV or cellphones before bed. Even small amounts of light can interfere with the body’s natural melatonin production.

He also suggests addressing anxiety, rumination, or bedtime fears directly. “Behavioral interventions, time and time again, have really been shown to be very effective,” Dr. Owens says. For younger children, that might mean learning to fall asleep without a parent in the room. For older kids and teens, it often means setting limits around devices and making sure the schedule they’re keeping is actually realistic.

Making a melatonin plan

Melatonin is a tool that works best with a plan behind it. Before starting, write down what problem you’re actually trying to solve. Is your child unable to fall asleep before 11pm? Waking during the night? Scared to sleep alone? Anxious about school?

A simple sleep log can make your conversation with your child’s doctor much more useful. For a week or two, track bedtime, approximate time asleep, any night wakings, morning wake time, screen use, and whether melatonin was used and, if so, at what dose. Dr. Owens calls sleep diaries “invaluable” because they reveal patterns that are nearly impossible to see when everyone’s tired and running on memory. That information helps you and your child’s doctor decide whether melatonin is worth trying, whether it’s working, and when it might be time to stop — keeping the focus not just on getting through tonight, but on helping your child build the sleep habits they’ll carry with them for years.

Frequently Asked Questions

Is melatonin safe for kids?

Melatonin is generally considered low risk and can be helpful for some children who have trouble falling asleep, especially when used short term and under a doctor’s guidance. But experts caution that there are still gaps in research about long-term use in kids, so it shouldn’t be treated as harmless or used casually without looking at underlying issues.

Can you OD on melatonin?

Accidental overuse can happen, especially because melatonin gummies may look like candy to young children. In recent years, there has been a major increase in poison control and ER visits related to accidental ingestion, so melatonin should always be stored like any medication — out of reach and ideally locked away.

Is melatonin bad for kids?

Melatonin is not inherently “bad” for kids, but it’s not the right solution for every sleep problem. If poor sleep is caused by anxiety, inconsistent routines, or a medical issue, melatonin may only mask the problem.

How much melatonin is safe for kids?

Experts recommend starting with the lowest effective dose. Some clinicians suggest starting with 1–2 milligrams for children ages four and up, and generally not exceeding 3 milligrams for kids ages six to 10 unless advised by a doctor.

The post Melatonin for Kids: Is It Safe? appeared first on Child Mind Institute.

ADHD Brain Marker Value in Doubt

Longstanding links between attention-related problems and changes in the brain’s cortex during childhood and adolescence could simply be due to developmental differences between the sexes, a study suggests.

The findings, in PNAS, showed that links between attention problems and slowed rates of cortical thinning were no longer evident after taking sex into account.

The results call into question proposals to use brain maturation patterns as biomarkers for attention deficit/hyperactivity disorder (ADHD) and related conditions.

More generally, they reveal the importance of accounting for sex differences during scientific investigations.

“For nearly two decades, delayed age-related cortical thinning has been widely viewed as a neurodevelopmental marker of attention-related psychopathology and ADHD,” reported Shannon O’Connor, PhD, from the University of Vermont, and co-workers.

“However, our findings suggest that this association may be largely confounded by sex differences in cortical development.”

Delayed thinning of the brain’s cortex—its outermost layer of grey matter—has long been proposed as a biomarker for ADHD-related conditions.

To investigate its value further, O’Connor and team studied 26,496 MRI scans from 11,025 adolescents.

The team initially found there was a link between attention problems and reduced rates of age-related cortical thinning across predominantly frontoparietal regions. Reduced rates of age-related thinning were associated with higher scores relating to attention problems.

However, this link dramatically reduced after accounting for sex differences in cortical thickness trajectories.

There were no significant age and attention problem interactions on cortical thickness when the sexes were studied separately. Furthermore, the genetic risk of ADHD was also not associated with slowed thinning in this region of the brain.

“Taken together, these findings suggest that previously reported associations between attention problems and delayed cortical thinning are largely attributable to unaccounted-for sex differences in neurodevelopment,” the authors concluded.

“Our results call into question an influential framework in developmental neuroscience and psychiatry that has shaped clinical understanding of ADHD for nearly 20 years, underscoring that cortical maturation patterns should not be interpreted as biomarkers for attention-related psychopathology without rigorous accounting for sex-related variation in brain development.”

The post ADHD Brain Marker Value in Doubt appeared first on Inside Precision Medicine.