Tag: Cognitive focus and executive control

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In Huntington’s Mouse, Optogenetic Activation of VIP Neurons Restores Brain Function

Huntington’s disease is a devastating brain disorder in which damage to nerve cells leads to progressively worsening cognitive and movement abilities. While the genetic mutation responsible for the condition is well known, the details of how the disease disrupts brain circuits have not been clearly understood. Now, researchers have identified and tracked neurons involved in Huntington’s disease progression and used optogenetics to selectively activate these neurons and improve the debilitating deficits of the condition.

The study is published in Nature in the paper, “Restoring cortical disinhibition improves Huntington’s disease phenotypes.”

“This work shows that correcting specific imbalances in brain circuits can restore function, even in a complex neurodegenerative condition, and highlights the potential of targeting defined cell types to promote recovery,” said Takaki Komiyama, PhD, professor in the UC San Diego Departments of Neurobiology (School of Biological Sciences) and Neurosciences (School of Medicine).

Huntington’s disease is caused by a trinucleotide repeat mutation in the Huntingtin (HTT) gene. While the mutation is well known, the neural networks connected with the disease progression have been more elusive.

This work aimed to map the neural circuits that expose the networks involved at the onset and spread of the disease’s debilitating symptoms. In transgenic mice carrying the same mutation as human patients, the researchers evaluated how different types of brain cells in the motor cortex are affected in Huntington’s disease. Advanced imaging techniques allowed the researchers to track the activity of these cortical neurons as the disorder progressed.

The researchers found that the disease disrupts the balance of activity across different cell types, including cortical inhibitory neurons.

“Cortical inhibitory cells have received little attention in Huntington’s disease, as for a long time they were considered to be spared from neurodegeneration,” said Irina Dudanova, PhD, previously based at the Max Planck Institute for Biological Intelligence, now at the University of Würzburg in Germany. “Surprisingly, we detected profound changes in their activity, with some cell types being overactive and some nearly silent.”

Huntington's
The activity of neuron types in the brain is imbalanced in mice with Huntington’s disease. The image depicts an example field-of-view from inhibitory (left) VIP (vasoactive intestinal peptide) neurons and excitatory (right) neurons recorded during behavior. Activity traces from a selected neuron for each type are shown above the images. [Sonja Blumenstock, Komiyama Lab, UC San Diego]

In particular, a class of inhibitory neurons known as vasoactive intestinal peptide (VIP) neurons, exhibited significantly reduced activity. VIP neuron activity is essential for normal learning, as these cells enable the brain to adapt and refine brain circuits during learning.

Reduced VIP neuron activity, the researchers reasoned, could be impairing the brain’s ability to function and learn properly. They sought to activate these cells to re-engage brain states that support learning. They tested this idea using optogenetics to stimulate VIP neurons.

“By activating the VIP inhibitory cell type, we gradually restored more normal activity patterns, and, very importantly, we also saw an improvement in the ability of the mouse to learn a motor task,” said Sonja Blumenstock, PhD, assistant project scientist at UC San Diego.

The results confirm VIP neurons as a key point of vulnerability in Huntington’s disease as well as a promising target for therapy. As to how this process works, the results suggest that modulating VIP neurons opens a “gate” that enables learning-related brain plasticity.

“This intervention restored more normal patterns of activity in the brain and improved movement in affected mice,” said Komiyama. “Importantly, the improvements persisted for days after stimulation ended, suggesting that the treatment triggered lasting beneficial changes in brain circuits rather than only temporary effects.”

The study provides important indications of where research could focus to normalize human brain function and facilitate brain recovery. Komiyama envisions a future scenario in which scientists could non-invasively activate the brain from outside the skull using novel approaches.

“Our study shows that despite the genetic defect, a precise intervention into the brain circuitry can lead to significant improvements in motor symptoms,” said Dudanova. “If we know which cells to target, we can retune the brain’s abnormal activity patterns. This gives hope for future therapies.”

The research also shows that corrections to specific brain circuit imbalances can restore function in a highly complex neurodegenerative condition, with similar potential in other disorders.

“We have come up with a way to allow the diseased brain to learn better,” said Komiyama. “The approach can improve behavior in diseased mice, and our hope is that a related approach will help people with impairment in their learning abilities.”

The post In Huntington’s Mouse, Optogenetic Activation of VIP Neurons Restores Brain Function appeared first on GEN – Genetic Engineering and Biotechnology News.

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LLMs are stuck in a groupthink groove. This startup is trying to get them out.

Let’s start with a game. Open up your chatbot of choice—Claude, ChatGPT, Gemini—and type “Give me a random number between 1 and 10.” You’re going to get 7. Almost always. Now type “Another” and you’ll get 3 or 4. Type “Another” again and you’ll get 8 or 9.

That won’t work every time—but if it did for you, you may wonder if I have superpowers. I don’t.

The truth is that most large language models are stuck in a rut. They are far more predictable and far less creative in their responses than you might expect. That’s fine for tasks like coding or research, but groupthink is a problem when you’re brainstorming or planning your next vacation.

The Australian startup Springboards has a solution. It built an LLM called Flint, which has been trained to come up with a wider variety of responses than mainstream LLMs to open-ended questions such as “Where should I go in Europe?”

“Most language models are fighting hallucinations,” says Springboards cofounder and CEO Pip Bingemann. “We welcome them.”

Bingemann introduced me to the random number game when he first showed me his company’s new model. It felt like watching an illusionist with a deck of cards. “This is our sales trick, and it works every single time,” he says.

After ChatGPT and Claude both gave their 7s, Bingemann turned to Flint. It too came back with 7: “Aha, of course that was going to happen, but it’s okay—7 is a legitimate answer.” He restarted the session and prompted again: ChatGPT gave 7, Claude gave 7, Flint gave 3.7916.

Run your way

It’s not just numbers. When Bingemann asked ChatGPT and Claude to name a type of car, he predicted that it would be a Toyota or a Honda—and he was right. Flint came up with a Ford F-150. “There’s all this lost information that doesn’t get served up in these models,” he says. “They’re just as capable of saying a Buick or a Tesla. They just don’t—they’re biased.”

Bingemann sent one last prompt to each of the three models: “Give me a tagline for a campaign for New Balance running shoes. Just the tagline.” Claude: “Run your way.” ChatGPT: “Run your way.” Flint: “Built to last, run to win.” It won’t win any awards, but at least it’s different.

This weird limitation of LLMs is starting to get more attention. In November a team of researchers put out a paper, titled “Artificial Hivemind: The Open-Ended Homogeneity of Language Models (and Beyond),” that exposed a remarkable degree of repetition not only in the answers from individual LLMs but between them as well. They found that different LLMs converged on very similar answers when prompted with open-ended questions.

It’s not clear exactly why this happens, but the researchers speculate it’s because most LLMs today are trained in similar ways on similar data to do similar tasks. The team won the best paper award at NeurIPS, a major AI conference.

When the researchers asked 25 different LLMs (including models from the top US firms as well as open-source models from China and elsewhere) 50 times each to write a metaphor about time, most of the 1,250 responses were a version of “Time is a river” or “Time is a weaver.”

(I asked some of my colleagues the same question and six people gave me six different answers. My highlight: “Time is a favorite sweatshirt, shaped by a lifetime of wear.”)

When you look for it, you see repetition everywhere, says Kieran Browne, cofounder and CTO at Springboards. “The way that most chat interfaces are designed, it makes it feel like you’re having a personal conversation,” he says. “I think most people don’t really realize the extent to which they are getting the same stuff as everybody else.”

Take another example: “What should I name my band?” Most models will say something involving “glass,” “neon,” “velvet,” or “static,” says Browne.  

When I tried it, ChatGPT spat out a list of 56 band names. At the top was “Glass Harbor.” Skimming through, I found “Static Empire,” “Neon Hearts,” and “Velvet Echo.” I asked Gemini; it gave me 15 suggestions, including “Static Horizon.”

Some of the suggestions looked pretty cool, though. ChatGPT’s “Sofa Astronauts” caught my eye, so I googled it—and found that a band called Sofa Astronauts already exists. 

(OpenAI says that training models to give reliable and coherent answers can lead them to converge around familiar, high-probability responses and that pushing harder for novelty can lead to weaker or less reliable responses. It also notes that the “Artificial Hivemind” paper studied models from 2024 that have since been updated.)

Creative catapult

Springboards has developed a tool backed by a selection of LLMs, including ChatGPT and Claude, that creative professionals in advertising or marketing can use to brainstorm ideas. The tool lets you drag around text produced by different models, picking the bits that you like and combining them into something new—in theory. Springboards is pitching Flint as an alternative model that users of its tool can select when looking for more variety.

Zoe Scaman, founder of the business strategy startup Bodacious and chief strategy officer at 77X, a direct-to-fan marketing platform set up by Luka Dončić of the LA Lakers, has been trying it out. “I find it really useful for throwing me in completely different directions,” she says. “I use it if I want to catapult myself all over the place.”

In one test, Scaman pitted Flint against Claude, Gemini, and ChatGPT by giving each of the models a classic MBA case study: How would you reinvent a finance company for today’s youth? The three mainstream models all went down the same path, she says: “You know, we need to teach financial literacy in a fun and funky way—well, that’s nothing new.”

But Flint came up with something different, suggesting that the whole concept of wealth accumulation should get a rebrand. “That was really interesting,” says Scaman.

She notes that Flint is still a prototype and doesn’t work all the time. “It sometimes falls over when you start pushing it too far,” she says. “But I think that the premise behind it is really powerful.”

Taking the temperature

Springboards built Flint on top of Qwen 3, an open-source model from the Chinese tech giant Alibaba. “We’re a small team,” says Browne. “Training a foundation model is not on the table for us. It’s just too expensive.”

Most LLMs have settings that let you adjust the level of randomness in their output. The most common is called temperature. “Obviously, that was one of the first things we explored, because that’s what people tell you: If you want more creativity, you turn up the temperature,” says Browne.

But changing those settings can also make models incoherent. Dialing up the temperature on one of OpenAI’s models to its maximum setting made it produce responses that switched from English into code halfway through a sentence, says Browne.

Springboards realized that parameters were blunt instruments for what it wanted to do. It does not make sense to dial up the randomness across the board; you only want to boost it at specific points in its output, he says.

For example, when you ask a chatbot “Where should I go in Europe?” the model only needs to tweak the randomness just before it names a destination, not for every word in its response.

To make Flint do this, Springboards trained its version of Qwen 3 to identify the points in its output where more variety was possible and fill those spots with words or phrases that were a little more random.

“Flint’s programmed to throw an oddball in. It’s more of an invitation to think wider,” says Maximilian Weigl, cofounder and chief strategy officer at Uncommon, a marketing firm. “That’s super interesting.”

Weigl’s team uses Flint alongside ChatGPT, Claude, and Gemini. “You can’t really create something boundary-breaking with tools that pull you back to the average,” he says. 

And yet Weigl notes that nine times out of 10 the average is fine. You don’t always need to reach for extremes with something like Flint, he says: “Most people are fine with good enough. They want to see mass-market familiar things.”

Weigl also cautions against using any LLM too much. “I have a big problem when people rely on the output from any AI, including Flint,” he says. “If I saw people on my team copy-pasting something from AI, I’d be like, ‘That’s not your job! Think, talk to other people, use your own voice.’”

For now, Flint is aimed at advertisers and marketers because those are Springboards’s customers. But Bingemann and Browne insist that a lack of variety is a problem for anyone using chatbots.

The idea is to give people the choice and leave it to them to decide if the result is good or not, says Bingemann. “Variety is great when you’re trying to spark ideas,” he says. “Let’s go down this route instead of letting the machines do it all and ending up in a gray, boring world.”

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Stigma and quality of life in hospitalized schizophrenia patient-family caregiver dyads in Northern China: an actor-partner interdependence model analysis

BackgroundSchizophrenia is a chronic and relapsing mental disorder that is consistently associated with a severely diminished quality of life (QoL) for patients. Existing research has predominantly focused on how the stigma experienced by patients with schizophrenia relates to their own QoL. However, stigma among family caregivers has received considerably less attention, and its potential association with patients’ QoL, in particular, remains underexplored. Therefore, this study aims to systematically analyze the dyadic associations of stigma—as experienced by both patients with schizophrenia and their family caregivers—with QoL, utilizing an actor-partner interdependence model (APIM). Through this framework, this study seeks to explore the interdependence of stigma between patients and their family caregivers and its correlational links to their quality of life.MethodsTwo hundred and sixty-four pairs of schizophrenic patients and their family caregivers were included, and the subjects’ stigma was measured using the Internalized Stigma of Mental Illness Scale and the Conjunctive Stigma Scale, respectively, and the quality of life was measured using the World Health Organization Quality of Life Measurement Short Form. The actor-partner effect of stigma on quality of life was explored by constructing an actor-partner reciprocity model.ResultsThe actor effect of stigma on quality of life was significant for people with schizophrenia and their family caregivers (β=-0.472, p < 0.001, β=-0.779, p < 0.001), and the partner effect of stigma on quality of life was significant for people with schizophrenia and their family caregivers (β=-0.128, p = 0.033, β=-0.419, p < 0.001).ConclusionIn future research and interventions aimed at improving the quality of life for people with schizophrenia and their caregivers, it is important to consider not only the individual’s own stigma, but also how the other person’s stigma is associated with one’s quality of life.
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What Are Intrusive Thoughts?

When a child confesses a frightening thought that seemed to come out of nowhere — “What if I hurt someone with this knife?” “What if mom dies in a car accident?” “What if germs get into this paper cut and I die of an infection?”  — you can both find it confusing and disturbing.  But in most cases these intrusive thoughts are not evidence of a problem.

Intrusive thoughts are unwanted ideas, images, or urges that pop into the mind seemingly out of nowhere. They might feel embarrassing, violent, sexual, or just plain strange — and they feel completely out of character, which is exactly why they’re so upsetting. “An intrusive thought is a lot like your brain sending junk mail,” says Theresa Welles, PhD, a clinical psychologist and director of the Bubrick Center for Pediatric OCD at the Child Mind Institute. “Just because it shows up doesn’t mean it’s important or true or something you even want.”

It also doesn’t necessarily mean that a child has OCD or another mental health disorder. Though intrusive thoughts are associated with OCD — in which unwanted thoughts (called obsessions) drive children to perform rituals (called compulsions) to alleviate them — for many children they are just fleeting thoughts. It’s only when kids become unable to let them go that they are concerning. Another way to think about it, says Dr. Welles, is that “the brain’s job is to generate thoughts, the same way an apple tree’s job is to produce apples. Not every apple is perfect — some are misshapen or wormy. And not every thought is meaningful or worth paying attention to. Having a thought is not the same as wanting it or intending to act on it.”

Who has intrusive thoughts

“Everyone who has a brain has them,” says Caitlyn Downie, LCSW, director of trauma and resilience at the Child Mind Institute. “It’s part of the human existence.” A child might suddenly imagine something terrible happening to a parent, or a teenager might have a violent or sexual thought that feels shocking or shameful. Most of the time, these pass quickly — unpleasant, but easy enough to brush aside.

That’s the key distinction: not the thought itself, but what happens after it. The concern isn’t that the thought appeared — it’s how the child responds, how often it returns, and whether it starts getting in the way of daily life.

For some children — particularly those who are anxious, perfectionistic, or who have OCD — intrusive thoughts become “sticky.” Instead of passing through, the thought snags. The child starts paying attention to it, trying to figure it out or make it go away, which only makes it feel more powerful. “Young people lack the experience to recognize that thoughts aren’t the same as intentions, desires, or actions,” Dr. Welles says. “The thoughts feel alarming. So the child pays more attention, and the more attention they give it, the more often it returns.” That loop of fear and self-doubt is what parents and clinicians need to be alert to.

When should parents be concerned?

Many children are too ashamed or frightened to describe what’s actually going on, so parents may never hear about the thought itself. Instead, changes in behavior are often the first clue. Look for signs like:

  • Increased distress, irritability, or moodiness
  • Avoidance of something that wasn’t previously a problem
  • Trouble concentrating or sleeping
  • Excessive guilt or repeated reassurance seeking
  • Rituals like checking, counting, washing hands, or going through routines in a specific way

It’s worth seeking professional support when intrusive thoughts are frequent and intense, hard to shake, causing real distress, or getting in the way of school, friendships, or daily routines.

Why intrusive thoughts feel so frightening

When an intrusive thought appears, it can set off the body’s alarm system — the same ancient survival mechanism that helped people run from danger or fight it off. In anxiety and OCD, that alarm bell rings when there’s no real emergency. The child has a thought, the body reacts with panic, and the child assumes the thought must be important because it feels big and important.

Children may also fall into what clinicians call thought-action fusion. “That’s the mistaken belief that having a thought makes it more likely to happen,” explains Dr. Welles, “or that it reveals something terrible about who they are.” A child who thinks, “What if I hurt my baby brother?” may become convinced the thought means they secretly want to — but intrusive thoughts are often the precise opposite of what a child would ever want. Paradoxically, Dr. Welles says, “for most people with anxiety disorders and OCD, these thoughts are the actual opposite of what they would ever do.”

How parents can help

The first thing to do is stay calm — harder than it sounds if the thought is violent, sexual, or taboo. Children look to their parents to gauge whether something is truly dangerous, so if you look horrified, your child takes that as confirmation the thought is something to fear.

When a child shares an intrusive thought, Downie suggests responding with warmth and curiosity: “Say something like, ‘I appreciate you telling me — it sounds like that was really scary.’ It also helps to normalize it: ‘A lot of people have thoughts they don’t particularly like.’” Some other responses that can help:

  • “That sounds really upsetting — I’m glad you told me.”
  • “Having a thought doesn’t mean you want it or that it’ll ever happen.”
  • “You don’t have to figure this out right now.”

The goal is to help your child feel less alone and less ashamed, without treating the thought like a five-alarm emergency. And do your best to avoid reassurance. Reassuring the child about the contents of a specific thought (for example, responding to a child who asks, “Are you sure I’m a good person?” with “Yes, you’re a good person”) can actually make things worse, especially in kids with OCD. They feel very temporary relief but then the thought creeps back and they need more reassurance. It becomes a cycle. Instead try: “I know this feels awful. And I know you can handle it.”

It also helps to redirect the child to something concrete: getting dressed, eating breakfast, watching a show, texting a friend. With younger kids, you might guide them in doing slow breaths or suggest they move to another room so they distract themselves from the thought. With teens, you might mean teach them to resist the urge to Google their fears or thoughts, confess, or ask the same question over and over again. “The idea,” Downie says, “is to validate the feeling without validating the fear. You’re saying: ‘I hear you, this is hard, and you can get through it.’”

What can cause intrusive thoughts?

Intrusive thoughts aren’t a diagnosis on their own — they’re a symptom that can show up across a range of conditions, or in children who have no diagnosis at all. Disorders they may be associated with include:

  • OCD: The most closely associated condition. Common themes include harm, contamination, sexual thoughts, and religious or moral fears.
  • Generalized anxiety: Tends to involve repetitive “what if” worries about everyday concerns — school, safety, family, the future.
  • Social anxiety: Brings intrusive thoughts about embarrassment, rejection, or being judged by peers.
  • PTSD: Can involve intrusive memories, images, or sensations tied to a traumatic event. “A child who has experienced trauma may worry about being harmed again or even about harming someone else,” Downie notes, “but that doesn’t mean every child with trauma will have intrusive thoughts.”
  • Depression: Often involves intrusive thoughts that fit a negative self-image: I’m worthless. I’m a burden. I’m a bad person.
  • Autism spectrum disorder: Repetitive thoughts often center on a special interest and aren’t typically unwanted or distressing the way OCD thoughts are — though they can look similar from the outside.
  • Psychotic disorders: Young people with psychosis tend to experience intrusive thoughts as fixed and real, without the self-awareness that typically accompanies anxiety-driven ones. Psychotic disorders such as schizophrenia are rare in children, though early signs can appear in the teenage years.

How intrusive thoughts are treated

Treatment depends on what’s driving the thoughts and how much they’re disrupting the child’s life:

  • For OCD, the gold-standard treatment is exposure and response prevention (ERP), a specialized form of cognitive behavioral therapy (CBT) where children practice sitting with intrusive thoughts without doing compulsions. Over time, they learn to tolerate uncertainty and discover that the thought, however uncomfortable, isn’t actually dangerous.
  • For anxiety, the same treatments are helpful. CBT helps children understand the connection between thoughts, feelings, and behaviors, and ERP helps kids learn to tolerate the anxiety these thoughts generate, and it gradually diminishes.
  • For trauma, treatment may include trauma-focused CBT. Mindfulness, DBT skills, and breathing exercises can also help regulate the nervous system.
  • Family involvement matters a great deal. “Parents often need help learning how to respond without accidentally feeding the anxiety cycle,” Dr. Welles says. SPACE (Supportive Parenting for Anxious Childhood Emotions) is an evidence-based approach that helps parents reduce accommodation and support their child’s brave behavior instead.
  • For moderate-to-severe OCD or anxiety, medication — typically an SSRI — may also be worth discussing with a psychiatrist or pediatrician.

Helping your child trust their own mind

One of the hardest things about intrusive thoughts is that they can make children afraid of their own minds — convinced that every thought needs to be examined or explained away before they can relax. But no one gets to have only pleasant, well-behaved thoughts.  

What children can learn is that a thought can be upsetting without being meaningful, loud without being true, and it can pass through without becoming a verdict on who they are. As parents, the most powerful thing you can offer is a calm, steady presence — taking it seriously without treating it as a catastrophe. When your child sees you aren’t panicked, they get to borrow some of that calm for themselves.

Frequently Asked Questions

What are intrusive thoughts?

Intrusive thoughts are unwanted ideas, images, or urges that pop into your mind unexpectedly. They often feel upsetting or out of character, but they’re essentially “junk mail” from the brain — not meaningful or important.

Are intrusive thoughts normal?

Yes, everyone can have them. Most children (and adults) experience intrusive thoughts at times, and in many cases they pass quickly without causing problems.

What causes intrusive thoughts?

They’re a normal byproduct of how the brain works, but they can become more frequent or “sticky” in kids who are anxious, perfectionistic, or dealing with conditions like OCD or trauma. Paying extra attention to the thought can also make it return more often.

Do intrusive thoughts mean I want to act on them?

No. Having an intrusive thought doesn’t mean you want to act on it or that it reflects who you are. In fact, these thoughts are often the opposite of what someone would ever want or do.

The post What Are Intrusive Thoughts? appeared first on Child Mind Institute.

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Treating ADHD With Methylphenidate (Ritalin, Concerta)

Methylphenidate is a stimulant medication used to treat symptoms of ADHD. It helps the brain regulate attention, focus, and impulsive behaviors.

It’s one of the two stimulants widely used in ADHD medications. Methylphenidate is the active ingredient in Ritalin and Concerta, among others. The other commonly used stimulant, amphetamine, is the active ingredient in Adderall and Vyvanse, among others. Both stimulants work by increasing levels of dopamine and norepinephrine, chemicals in the brain that control attention, focus, and impulsivity. If a child doesn’t do well on the first stimulant medication they try, they may respond better to a different formulation of that type or the other type of stimulant.

How is methylphenidate different from amphetamine?

Methylphenidate is somewhat less powerful than amphetamine and tends to have milder side effects.

If your child is under 12 and has just been diagnosed with ADHD, a doctor is likely to prescribe a methylphenidate medication first, to see how well the medication reduces their ADHD symptoms, and whether the side effects are problematic.

Methylphenidate is also many doctors’ first choice for younger children because it has been used to treat ADHD much longer than amphetamine. Ritalin (methylphenidate-based) was FDA approved in 1955, while Adderall (amphetamine-based) wasn’t approved until 1996. In countries outside the United States, amphetamine-based ADHD medications are less widely approved than those based on methylphenidate.

How methylphenidate works vs amphetamine

The two stimulants target the same brain chemicals but work slightly differently, says Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. Methylphenidate increases the levels of dopamine and norepinephrine by blocking what’s called reuptake — the process by which nerve cells reabsorb these chemicals after they’ve been released. As Dr. Mitrani describes it, methylphenidate “enhances” the norepinephrine and dopamine the brain naturally releases by making the chemicals stay around longer. It boosts the stimulation the brain is already getting from whatever activity the child is engaged in.

Amphetamine, on the other hand, not only blocks reuptake but stimulates the release of more dopamine and norepinephrine, which is why it’s considered stronger. “Adding stimulation with amphetamine sometimes helps,” he notes. “But sometimes that added stimulation is too much, and it increases side effects the child experiences.”

Kids vary in how they respond to methylphenidate vs amphetamine

There is individual variation in how children respond to the two stimulants. So if methylphenidate doesn’t give the desired symptom relief or produces problematic side effects, it’s recommended practice to try amphetamine, or vice versa. Research shows that 70 percent of children with ADHD respond to a trial of methylphenidate. More than 90 percent will have a beneficial response to one of the stimulants if both methylphenidate and amphetamine are tried. Studies also show that approximately 41 percent respond equally well to both types of stimulant.

Children can also vary in their response to different formulations of the same stimulant, which affect the rate at which the medication goes into the bloodstream.  For instance, a short-acting form of Ritalin will kick in quickly and last for 3-4 hours, while Concerta, a delayed-release formula, lasts as long as 10-12 hours. It’s very common for kids to try several before finding the best fit.

What are the side effects of stimulant medications?

Methylphenidate and amphetamine have the same side effects, though they may be less intense with the former.

Appetite suppression

The most common side effect of stimulants is appetite suppression. It can be especially concerning with long-acting forms of the medication, which are often preferred to get better coverage through the school day. Kids who take a long-acting stimulant in the morning tend to lose their appetite for lunch and may not be interested in eating until after dinnertime.

When this is a problem, Dr. Mitrani notes that taking a shorter-acting form of the medication can help. “For instance, Concerta is a methylphenidate medication that lasts for a long time and can suppress appetite for 10–12 hours.” An alternative might be a medication that lasts for 6–8 hours, such as Metadate CD or Ritalin LA. Some children with more pronounced problems with appetite will do better on a short-acting dose in the morning and then another after lunch, he adds, since it gives them a break during the day where they can eat better.

Sleep issues

Kids who take stimulant medication can have trouble falling asleep. This can happen when a long-acting medication or an afternoon dose of a short-acting medication wears off and they get restless or hyperactive around bedtime. Difficulty falling asleep can get better after a few weeks, but if it doesn’t, it may be helpful to change either the timing or the type of the medication that is given. It’s also important to explore whether there are other contributors to sleep challenges, such as worry, screen time too close to bedtime, or lack of a consistent evening routine that helps kids calm down.

Irritability

Stimulant medications can generate agitation and irritability, which can be especially problematic in kids who are already anxious. For children with anxiety, this can be another reason to start treatment with methylphenidate, because amphetamines can feel more activating.

But Dr. Mitrani notes that treating ADHD can also reduce anxiety: “Some kids are so stressed about school — because they can’t pay attention or arealways getting in trouble — that when you treat the ADHD, they are better able to manage the demands of school and become less anxious.”

That reduction in school anxiety can also affect what happens when they get home from school. “When there is anxiety, it’s like kids are holding it together at school, and then they come home after a stressful day and just let it out,” he says. “So if the school day is less stressful, you may also see that come down at the end of the day.”

Mood changes

Some children report that stimulant medications seem to dull their personality. Dr. Mitrani suggests that this may be connected to the medication stimulating the prefrontal cortex, the part of the brain that not only manages attention and focus, but also helps regulate emotions and impulse control in other brain areas. “Enhanced control of the emotional part of the brain can cause this feeling of dullness,” he notes. “Some people will even say they feel depressed, that they’re just not like themselves because they don’t have the same energy or personality.”

If this happens to a child on methylphenidate, Dr. Mitrani will recommend trying an amphetamine or a non-stimulant medication.

Rebound effects

Some families report that their child is irritable or emotional after school or at the end of the day, when the stimulant medication is wearing off. Dr. Mitrani notes that this can coincide with the child being hungry after missing lunch. It can also be connected to the medication level dropping too quickly, and strategies that create a more gradual decrease may help take it away. For example, he might suggest adding a small dose of  short-acting form of the stimulant a half hour before the morning medication wears off.

Starting children on methylphenidate

Dr. Mitrani usually starts a child on a short-acting form of methylphenidate for two reasons: as a quick test to see if the child will experience side effects and to have an opportunity to try it twice in a day, to have more chances to assess for positive changes.

He recommends starting the medication on a weekend or a break from school and giving the child some tasks that are challenging for them because of their ADHD, like reading or something else that requires concentration, such as cleaning their room or doing household chores. “After lunch you want to try it again, to have another time point to check on. Because if you only give one dose of the medication, you don’t know if the child’s behavior was a result of the medication or some other factor. The more data points that we have, or more trials, the more information we get.”

He recommends keeping the child on short-acting doses for at least several days before trying a longer-acting formula.

Starting children on a low dose

Practice guidelines for psychiatrists recommend starting children on a low dose to assess any side effects the child might experience and gradually increasing it over 1-2 weeks with careful monitoring of response until you reach the minimum dose that will give the best symptom relief.

There is a great deal of variation in how children respond to these medications, so starting with an “average” effective dose, even adjusted by body weight, would be under-medicating some kids and overmedicating others.

For instance, for a 6- or 7-year-old child, a common starting dose of a short-acting medication might be about 2.5 mg, going up to 5 mg if more is needed for symptom relief and side effects are not an issue, Dr. Mitrani says. 

Liquid versions of either stimulant have an advantage when it comes to getting exactly the right dose, he notes: “You can do, 1 milliliter, 1.5, 1.6, depending on the syringe.”

Long-acting formulations that come in capsules can be especially frustrating, he adds — since they come in set doses and can’t be opened and divided effectively, because the beads inside are made to be triggered at different time periods.

Trying different formulations

Dr. Mitrani stresses that small differences in the formulation of a medication can make a difference in a child’s reaction.

For instance, Focalin (dexmethylphenidate) is a refined form of methylphenidate. Standard methylphenidate medications contain two mirror-image forms, or isomers, but most of the benefit comes from one of them. Focalin contains only this more active isomer. For some children, it works better, causes fewer side effects, or feels smoother.

He also notes that variations in the release patterns among long-acting formulations can affect a child’s experience. “Take Concerta, which has a unique mechanism for the extended release,” he explains. “There are three phases: a really immediate phase, then a regular Ritalin kind of phase and, then a slow extrusion of the remaining methylphenidate throughout the day that helps it last as long as 12 hours.”

By contrast, he describes Ritalin LA, which tends to last for 6-8 hours, as “50-50” — 50 percent of the dose is immediate released and the other half is delayed release. Other formulations are “40-60” or “30-70.” “These subtle differences can result in some kids responding better to one than the other, while other kids can do well on any of them.”

So even within the methylphenidate group, there may be reason to try a child on number of different formulations to get the best fit. And, of course, other reasons for trying different versions are limits on what insurance covers —which can change suddenly — and what’s available because of shortages. “And that can be really frustrating for families,” he says. “What I hear is, ‘My child was on Concerta or on Metadate CD and they made me switch to this one and now my kid’s not doing as well.’ “


When families cannot get a medication that has been working, finding another medication that’s available, that’s effective, and that insurance will approve can be a lot of hoops to jump through, he adds.

The post Treating ADHD With Methylphenidate (Ritalin, Concerta) appeared first on Child Mind Institute.

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Subjective sleepiness and objective sleep propensity in adults with attention-deficit/hyperactivity disorder referred for multiple sleep latency testing

IntroductionAdults with attention-deficit/hyperactivity disorder (ADHD) often report excessive daytime sleepiness, but the relationship between subjective sleepiness and objective sleep propensity remains unclear. We examined this relationship in adults referred for Multiple Sleep Latency Test (MSLT) evaluation, using a clinical comparison group with excessive daytime sleepiness (EDS) but without ADHD.MethodsIn this retrospective cross-sectional study, we analyzed medical records of 130 adults aged 18 years or older who underwent MSLT between January and December 2021, including 68 adults in the ADHD group and 62 in the EDS-only group. Subjective sleepiness was assessed by the Epworth Sleepiness Scale (ESS) and objective sleep propensity by mean MSLT sleep latency, with MSLT positivity defined as mean sleep latency ≤ 480 s. Associations between ESS scores and mean sleep latency were assessed within each group, and correlation coefficients were compared between groups using Fisher’s r-to-z transformation.ResultsESS scores did not differ significantly between groups, with median scores of 14.0 in the ADHD group and 13.0 in the EDS-only group. In contrast, objective sleep propensity differed significantly: median mean sleep latency was longer in the ADHD group than in the EDS-only group (432.0 s vs 322.0 s, p = 0.008), and MSLT positivity was less frequent in the ADHD group (61.8% vs 87.1%, p = 0.001). Within the ADHD group, ESS scores were not significantly correlated with mean sleep latency, including among MSLT-positive cases. A significant inverse correlation was observed in the MSLT-positive EDS-only subgroup, although formal comparison of correlation coefficients did not demonstrate a statistically significant between-group difference in the ESS–MSLT relationship. SOREMP frequencies were numerically higher in the EDS-only group but did not differ significantly between groups.DiscussionThese findings suggest that subjective sleepiness complaints and objective sleep propensity may not closely align in adults with ADHD referred for sleep evaluation, and support the need for integrated psychiatric and sleep-medicine assessment when such patients present with excessive daytime sleepiness.
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Associations of TNF-α, MIF, and cortisol with cognitive function in patients with bipolar disorder during acute manic episodes: a short-term follow-up study

BackgroundBipolar disorder (BD) is frequently accompanied by cognitive impairment, and growing evidence suggests that immune-inflammatory activation and hypothalamic-pituitary-adrenal axis dysregulation may contribute to its pathophysiology. This study aimed to examine the associations of tumor necrosis factor-α (TNF-α), macrophage migration inhibitory factor (MIF), and cortisol (COR) with cognitive function in patients with BD during manic episodes and to characterize their short-term changes.MethodsIn this short-term follow-up study, 53 patients with BD during manic episodes and 53 healthy controls (HCs) were enrolled. Plasma TNF-α, MIF, and COR levels were measured using enzyme-linked immunosorbent assay. Cognitive function was assessed using the Chinese Brief Cognitive Test, including information processing speed (IPS), executive function (EF), sustained attention (SAT), and working memory (WM). Patients were evaluated at baseline and after 8 weeks of treatment, whereas HCs were assessed once at baseline. Group comparisons and biomarker–cognition correlation analyses were performed. Multiple testing in the correlation analyses was controlled using the Benjamini–Hochberg false discovery rate (FDR) procedure.ResultsAt both baseline and follow-up, patients with BD had significantly lower IPS, EF, SAT, and WM scores, but significantly higher plasma TNF-α, MIF, and COR levels, than HCs. After 8 weeks of treatment, cognitive scores in the BD group improved significantly, whereas reductions in TNF-α, MIF, and COR did not reach statistical significance. In exploratory unadjusted Pearson analyses, several biomarker–cognition associations survived FDR correction. However, in the primary adjusted partial correlation analyses, only the negative association between TNF-α and WM remained significant after adjustment for covariates and FDR correction at both baseline and follow-up.ConclusionPatients with BD during manic episodes exhibited widespread cognitive impairment accompanied by elevated inflammatory and neuroendocrine markers. TNF-α showed the most robust association with working memory after adjustment for covariates and correction for multiple comparisons. Associations involving MIF or cortisol and executive function should be interpreted as exploratory and require validation in larger longitudinal studies.