Tag: ADHD

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Understanding the Different Types of Psychological Evaluations

If your child is struggling with mental health, behavior, or learning challenges, the first step to getting them the support they need is to seek a professional assessment. Whether you’ve been motivated to do so by the child’s teacher, the school, or your own concerns, there are several types of evalutations to choose from. And it can be hard to tell which one would be the best choice for your child.

There are three main types of evaluations: diagnostic, psychoeducational, and neurospychological.

A diagnostic evaluation is typically all you need for your child to receive a diagnosis of a mental health disorder and start a treatment plan.

A psychoeducational assessment is an evalution typically performed through a school’s Committee on Special Education (CSE) to see if a child qualifies for accommodations. This usually includes cognitive and academic testing, as well as social-emotional rating scales.

A neuropsychological evaluation is the most complete assessment of a child’s overall social-emotional, cognitive, academic, and neuropsychological functioning (including language, visual-motor, attention, executive functioning, and learning and memory skills). It’s especially useful for children with complex symptoms or learning challenges.

If you are looking to determine whether your child has a learning disorder, they’ll typically need either a full neuropsychological evaluation or one targeted for a specific learning disorder.

Preparation

For any of the three types of evaluations, it’s suggested that you do the following in advance:

  • Gather documents: Before the first visit, you will need to collect any relevant health and behavior records for your child, which could include medical records, past evaluations, school reports, and developmental screenings conducted by the child’s pediatrician.
  • Record observations: Take note of your child’s behaviors, especially when they seem atypical or out of character. Keep track of when they occur, as well as how frequently. This will be helpful for the evaluator to know.
  • Bring snacks and water: Since these examinations take several hours, you and your child will most likely need to take breaks.

Diagnostic evaluation

What it is: A diagnostic evaluation is a focused assessment to determine whether your child meets the criteria for a specific mental health or neurodevelopmental disorder — including depression, anxiety, ADHD, or autism. For example, if your child struggles with intrusive thoughts that make them anxious and they develop rituals to keep their anxiety at bay, a mental health professional will most likely add specific testing for OCD to their evaluation.

Purpose: “Diagnostic evaluations are primarily the gateway for receiving treatment,” explains Adam Zamora, PhD, a senior neuropsychologist and director of the Gund Learning and Diagnostic Center at the Child Mind Institute. “We want to know what diagnostic criteria they meet to figure out which treatment would be best for that diagnosis.”

Qualified provider: Typically, the evaluation is conducted by a clinical psychologist, psychiatrist, or another qualified mental health professional.

Time commitment: The evaluation process is about 4 hours total. This includes an interview with parents that will take 1–2 hours, a one-hour session with the child, and a one-hour feedback session with the family.

Evaluation process:

  • The clinician will collect information about your child’s developmental history as well as your family history. So they’ll usually speak to any previous treatment provider your child has had as well as their teacher, says Dr. Zamora. Then you’ll be interviewed, which can be done virtually.
  • You will fill out questionnaires about your child’s daily habits and behaviors. And you’ll fill out a rating scale that will help to quantify your child’s symptoms and compare them to the norm. This can be helpful for balancing out the information received during the interview, says Dr. Zamora. “I’ve had some parents tell me that their kid has all these significant challenges. And then they fill out the rating scales and everything is within age expectation. Or it can be the other way around.”
  • Then the child comes in for observation and evaluation. A parent could be present, depending on the situation, notes Lara Litvinov, PhD, a senior psychologist and director of the ADHD and Behavior Disorders Center at the Child Mind Institute. During this observation, the clinician will administer standardized assessments, which typically are tailored to their symptoms. For instance, if it’s thought that a child may have autism, they will be tested on their social communication skills and whether they show repetitive behaviors. The evaluator might observe if the child has difficulty maintaining eye contact as they talk, or see if they play with toys in the exact same way over and over again. If it’s thought that a child may have ADHD, the clinician will test their cognitive and executive functioning abilities. They might have the child solve puzzles or play memory games.
  • Once the clinician has been able to review the information collected from the evaluation, there will be a feedback interview. Along with a diagnosis, the clinician will provide their recommendations for treatment. They will also suggest further testing if necessary.

Report: Shortly after the feedback interview, you will receive a formal written report of the evaluation results. This will consist of brief background information, a diagnosis, and recommendations.

Cost: Depending on the location, clinician experience, the specificity of testing, and insurance coverage, these evaluations can range from $300 to $4,000. Community health centers may offer lower rates, while a private practice with licensed psychologists or psychiatrists will charge more.

Drawbacks: While a diagnostic evaluation is good for starting treatment, it doesn’t provide an in-depth look at all aspects of your child’s brain functioning. If a child’s symptoms are complex, they’re thought to have a learning disorder, or they’re struggling with multiple mental health disorders, it may be more helpful to have a neuropsychological evaluation (see below). Typically, the evaluator will let you know if they think your child needs further assessment.

Psychoeducational evaluation

What it is: A psychoeducational evaluation determines if a student is eligible for special education or accomodations at school. It’s an assessment of their cognitive, academic, social, and emotional functioning compared to other children the same age. It also lets the school know the type of services the child will need.

Purpose: Children with mental health and learning disorders often need accommodations and services at school to have the same opportunities as children who don’t have these challenges. They could get this through an Individual Education Program (IEP) or a Section 504 plan. Since a school needs to determine that a student’s academic abilities are significantly impaired, an existing diagnosis may not be enough. Many schools require a psychoeducational assessment within a certain window of time after receiving a referral from a medical provider or a formal written request from you.

Qualified provider: This evaluation is conducted by a registered school psychologist.

Time commitment: The evaluation can take 4–6 hours in total. You and your child may be asked to come in for a whole school day or for separate sessions over the span of a few weeks. The testing can be stressful for the child, Dr. Litvinov explains, so it can be helpful to break it up into several sessions.

Evaluation process:

  • In addition to the health records you provide, the psychologist will have asked your child’s teachers to complete a questionnaire about their learning and behavior.
  • The psychologist will interview you about your child’s academic and developmental background, family history, and any concerns you have. You will likely be asked questions about how your child handles school assignments, what their academic strengths and weaknesses are, as well as notes you’ve received from their teachers. If your child is under 10, the examiner likely will ask you to fill out questionnaires about your child’s social-emotional and behavioral functioning.
  • The psychologist will then evaluate your child for several hours. You won’t be permitted in the room with them, but you can wait outside.

What’s tested:

Cognitive functioning: These assessments often include verbal or visual tests to examine verbal and nonverbal reasoning, certain types of memory, and the speed at which your child processes and responds to information. They will also be asked to engage in problem-solving tasks.

Social and emotional functioning: The child’s parents and teachers will complete questionnaires to gauge their social and emotional functioning. Depending upon the child’s age, they may fill out their own questionnaires as well.

You will then have a feedback session with the psychologist. Depending on their age, your child can be included in this session. During this time, you will go over the results, which can identify your child’s learning strengths and challenges and recommended supports.

In some cases, the evaluation may also result in a formal diagnosis of a specific learning or language disorder, depending on the professional conducting the evaluation and state licensing requirements.

Report: Both you and the school will receive a written report that includes detailed results, and provide suggestions for accommodations and interventions needed. It will also say if your child is eligible for separate special education classes.

Cost: The evaluation is free if it is conducted by the school. You will only need to pay out of pocket if you seek a private assessment. This can cost between $1,000 and $6,000. Your insurance may cover some of it, depending on your provider.

Drawbacks:

Given its purpose, this evaluation focuses only on academic skills, learning, and how your child performs in school. In many states, including New York, a school psychologist can’t give a formal diagnosis, Dr. Zamora adds. A psychoed assessment may not be comprehensive enough to highlight all key challenges your child may be experiencing.

Additionally, there could be delays in getting an assessment due to a backlog in requests or a shortage in school psychologists. School officials could also refuse to provide one altogether if they determine your child is not qualified based on specified criteria.

Neuropsychological evaluation

What it is: A neuropsychological evaluation is the examination of a child’s overall social-emotional, cognitive, academic, and neuropsychological functioning — and how they affect each other. This is often recommended for children who have complex issues, where a diagnostic evaluation might be too narrow. It can be helpful for those with multiple mental health disorders, neurodevelopmental disorders such as autism and ADHD, learning disorders, or traumatic brain injury.

A neuropsychological exam takes several sessions, so it can provide a more complete, comprehensive picture of what might be going on. “We’re not just seeing one snapshot of a kid, but multiple snapshots,” Dr. Zamora explains. “And we’re sometimes looking to see if there is a very significant difference in how they’re performing on a Wednesday morning versus a Thursday afternoon, for example. So if you have a kid with ADHD or executive functioning challenges, they may seem okay one day. Then you test them on another day and they’re more inattentive or dysregulated, so you’re going to get a different presentation.”

Purpose: There can be several reasons for seeking this type of testing:

  • Learning disability or school accomodations: Both neuropsychological and psychoeducational assessments can be used to get a child accomodations at school, Dr. Litvinov says. But a neuropsychological evaluation can reveal underlying or more nuanced weaknesses that a psychoed evaluation missed, determining the child’s need for accomodations. So if you are unsatisfied with the assessment your child received or if you are unable to get one from the school, a neuropsych evaluation can be useful.
  • Complex symptoms: Sometimes a child displays challenges and behaviors that can relate to more than one mental health disorder. For instance, ADHD and anxiety can look similar in some children, so testing that covers a wider range of functioning may be needed to get to the bottom of the issues your child is dealing with — and identify the type of support they need. Trauma-related symptoms can also be difficult to pinpoint. “A lot of kids that I see have trauma. And there’s a lot of overlap of trauma symptoms and anxiety symptoms,” Dr. Litvinov explains. “You don’t want to be quick to judgment.”
  • Ineffective treatment: In some cases, a child may have received a diagnosis and has been getting treatment for a while, but it isn’t working. “We want to see if there’s something that we’re missing,” Dr. Litvinov explains. “And with older kids, they might be reporting less, so parents might know less.”
  • Flexibility: Sometimes, given cost and scheduling contraints, a family can request a more focused neuropsychological evaluation. “This looks like what I would call a beefier psychoed evaluation,” Dr. Zamora explains. “So if somebody came to us and was considering just testing for a learning disorder, I’d take a deeper dive into those academic areas to get a sense of which disorder it is. Is this actually dyslexia? Is it dysgraphia?” This evaluation usually takes 3–4 hours.

Qualified provider: This evaluation is typically conducted by a team of clinical psychologists, including a trained neuropsychologist.

Time commitment: The evaluation takes about 6–9 hours of testing in total, with 2–3 additional hours dedicated to interviews and a feedback session between you and the neuropsychologist. You and your child could be asked to come in for the whole day or separate sessions over the course of several days a week.

Evaluation process:

  • The clinican will look at medical records, school reports, and any previous evaluations. They may also speak directly to your child’s teacher and ask them to fill out questionnaires regarding your child’s learning abilities and behavior.
  • You will be interviewed about your child’s background, your family history, and concerns you have.
  • Your child will then spend one-on-one time with the neuropsychologist, in which they will be interviewed and given a series of assessments that examine the following:  
    • Cognitive and intellectual abilities
    • Short- and long-term memory and learning skills
    • Executive functioning
    • Speed and efficiency of processing
    • Concentration and attention
    • Language functioning 
    • Gross and fine motor skills
    • Visual-spatial skills
    • Emotional functioning
    • Social skills and social language
    • Academic functioning, including reading, writing, and math skills

Report: Afterward, you will receive a detailed written report that includes test results, interpretations, diagnoses, and recommendations. It can be used to support a request for a 504 plan or an IEP from your child’s school — and provide guidance to school staff on determining the right type of services for your child. The clinician may want to have a follow-up appointment to discuss the report and answer any questions you may have, but that is not always required.

Cost: Due to the time and depth of the evaluation, the cost of this testing can range from $1,500 to $10,000. While most evaluators may be out-of-network providers, there is a chance that a portion of this kind of evaluation may be covered by insurance.

Drawbacks: It can take a long time to schedule this test, as there is often a waiting list for child and adolescent neuropsychologists. This is also the most expensive examination out of the three.

Why knowing the difference is important

Dr. Litvinov emphasizes that it’s imperative that you’re aware of what each evaluation type entails. “I talk to parents whose child has received a diagnosic evaluation, and they’re frustrated or confused because they expected a detailed report that you typically get from a neuropsych evaluation,” she explains.

Some families wait months for a neuropsychological evaluation, not realizing that they can get treatment started for their child with a diagnostic evaluation or that a school can provide a free psychoeducational evaluation.

Understanding each type of evaluation will help you get your child the support they need.

The post Understanding the Different Types of Psychological Evaluations appeared first on Child Mind Institute.

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ADHD-related mental health and school impairments across educational stages: sex-specific patterns in Japanese youth

IntroductionWhile ADHD-related challenges are well-documented internationally, understanding of how these manifest across educational stages and sexes remains limited. This study examined mental health symptoms and school functioning in Japanese children with and without ADHD across elementary, junior high, and senior high school.MethodsIn this comparative cross-sectional study, parents of 1,594 Japanese children (797 with ADHD, 797 without ADHD) aged 6–18 years completed questionnaires assessing ADHD symptoms (ADHD-RS-IV), depression (SMFQ), anxiety (SCAS), irritability (ARI), bullying victimization, academic achievement, and social support. Three-way ANOVAs examined interactions between ADHD status, child sex, and educational stage, with Cohen’s d effect sizes calculated for group comparisons.ResultsChildren with ADHD demonstrated significantly poorer outcomes across nearly all domains, except for teacher support, with effect sizes ranging from moderate to very large (d = 0.35–1.44). Contrary to expectations, the largest group difference for girls’ depression emerged in elementary school (d = 1.44) rather than junior high school, and girls’ anxiety differences were comparably large in elementary (d = 1.25) and junior high school (d = 1.30). Girls with ADHD showed consistently larger effect sizes than boys for depression (mean d: 1.14 vs. 0.84), anxiety (1.13 vs. 0.73), and irritability (1.32 vs. 0.90) across all stages. Significant ADHD × sex interactions emerged for depression, anxiety, and irritability. Bullying victimization affected 31.0% of children with ADHD compared to 7.5% of non-ADHD children, with peak effects in elementary school. Academic difficulties showed the anticipated pattern of increasing impairment from elementary to junior high school, particularly for boys (d = 0.65 to 1.07).DiscussionThese findings reveal pronounced sex differences in ADHD-related mental health burden, with girls experiencing what may be a “hidden burden” of greater internalizing symptoms across development. The smaller group differences for internalizing symptoms in adolescence may partly reflect decreased parental awareness of adolescent internalizing symptoms. These results underscore the need for sex-specific, developmentally-informed interventions with particular attention to early identification and support for girls with ADHD who may be overlooked in clinical and educational settings.
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What Is Guanfacine?

Guanfacine is a non-stimulant medication that is FDA-approved to treat ADHD in children and teens. It can also be used off label to treat tic disorders and symptoms of autism.

Guanfacine is not as powerful in reducing ADHD symptoms as stimulant medications, but it’s especially helpful for children who are hyperactive and impulsive — who can’t sit still in class, blurt out answers, interrupt, melt down easily, or have trouble shifting gears. 

“I always describe guanfacine as a behavioral medication,” says Paul Mitrani, MD, PhD, a child and adolescent psychiatrist at the Child Mind Institute. It can help kids who struggle to regulate their impulses and emotions take time to pause before acting.

What is guanfacine?

Guanfacine is a kind of medication called an alpha-2A adrenergic receptor agonist. Alpha-2 agonists — including guanfacine and clonidine, among others — were originally developed to treat adults with hypertension, or high blood pressure. But guanfacine may be best known as a treatment for ADHD.

Guanfacine (under the brand name Intuniv) was officially approved to treat ADHD in children in 2009 but has been used for this purpose since the 1990s.

How does guanfacine work?

The alpha-2A receptors that guanfacine targets are found in various regions of the brain and nervous system, but heavily concentrated in the prefrontal cortex, the part of the brain that helps regulate attention, emotion, impulsivity, and behavior.

Researchers don’t fully understand how guanfacine works, but it is thought to act by enhancing the functioning capabilities of those alpha-2A- receptors in the prefrontal cortex, improving a person’s ability to focus “above the noise” of the environment.

Guanfacine also has a calming effect by acting on alpha-2A receptors in the sympathetic nervous system, reducing sympathetic nerve impulses. This calming effect is especially helpful for hyperactivity and impulsivity. (The sympathetic nervous system also regulates blood pressure, thus the drug’s original use.)

Guanfacine and ADHD

Guanfacine can be used to treat ADHD on its own, but it is commonly used in addition to a stimulant.

The first-line medication treatment for ADHD, for both children and adults, is a stimulant medication like methylphenidate (Ritalin) or amphetamine (Adderall). Guanfacine, however, is a non-stimulant drug — it can target the same symptoms, it just goes about it in a different way.

Still, Dr. Mitrani adds: “We don’t typically start with guanfacine as a medication for ADHD unless the behaviors are more of the problem or there’s concern about starting a stimulant.”

For example, guanfacine may be beneficial for a child who does well academically but has trouble settling down and following rules in class. “I see kids who are really bright, so they don’t have to pay full attention to do well in school but can still struggle with behaviors that are causing a problem,” says Dr. Mitrani. For other kids, “they may benefit from a stimulant for their attention and behaviors, but parents are concerned that a stimulant may result in them not eating, which can impact growth. That’s where I may start with guanfacine.”

For some children, adding guanfacine can also address issues associated with stimulant medications, including sleep problems and the “crash” in mood and behavior that some kids experience at the end of the day, when they’re coming off a stimulant. Guanfacine may make kids drowsy, so it’s usually taken at night, says Dr. Mitrani. That means it can offset side effects of a stimulant by helping kids get tired when it’s time for bed. But some kids take guanfacine in the morning without feeling sleepy during the day, he adds.

What are the side effects of guanfacine?

Sleepiness: A common side effect of guanfacine is sleepiness or fatigue. But if a child is really tired after taking guanfacine, says Dr. Mitrani, it’s probably not a great fit. “Tiredness is the one side effect we are most concerned with because if it makes you tired, it’s not a good medicine for you.”

If a child is taking guanfacine in addition to a stimulant, consider their whole medication schedule when discussing any concerns with their pediatrician. “For example,” says Dr. Mitrani, “if they don’t take their stimulant on the weekend, but they stay on the guanfacine, they may feel more tired on the weekends than they do during the week because the stimulant is helping balance things out.”

Low blood pressure: Guanfacine can also lower blood pressure, which can cause dizziness. “Most kids tolerate any small drop in blood pressure fine because their hearts are young and healthy and they compensate with an increased heart rate,” Dr. Mitrani says. But other possible side effects related to lower blood pressure (hypotension) include constipation, dry mouth, or headaches.

What are the different kinds of guanfacine?

There are two kinds of guanfacine: immediate-release (IR), which lasts for several hours, and extended-release (ER), which lasts all day.

Immediate-release (IR) guanfacine: Guanfacine IR (previously known by the brand name Tenex) is used off label to treat ADHD and other disorders. Guanfacine IR is absorbed faster, peaks earlier, and lasts for less time than the extended-release version. Children typically take more than one dose per day.

Guanfacine ER (Intuniv): Guanfacine ER is FDA-approved to treat ADHD in children ages 6 through 17, either alone or in addition to stimulants. Guanfacine ER is available in a range of doses, typically starting at 1mg, and is taken once per day.

Notes on dosing: The recommended pediatric dose of guanfacine ER is 1–4mg daily for children 6 to 12. Children 13 to 17 are FDA-approved to receive a dose up to 7mg. But some young children tolerate and benefit from doses above 4mg, says Dr. Mitrani. Still, any amount of the drug should be handled with caution. If a decision is made for a child to stop taking guanfacine, the dose should be tapered off over a period of time, usually several weeks. Stopping the medication abruptly, particularly at a higher dose, can cause a spike in blood pressure, Dr. Mitrani explains.

Short- and long-acting forms of guanfacine are not interchangeable in terms of dosing. For example, if your child is taking guanfacine ER 2mg, that doesn’t mean it would be appropriate for them to make a direct switch to guanfacine IR 2mg — these medicines are not equivalent because of the way they are absorbed. If a child switches medications, their dose must be adjusted.

Guanfacine vs clonidine

Guanfacine isn’t the only drug of its class that can be used to help with ADHD symptoms like hyperactivity or impulsivity. Another commonly used alpha-2 agonist is called clonidine (Catapres, Kapvay). Clonidine, FDA-approved to treat ADHD in children 6 to 17, essentially works the same way as guanfacine but tends to be a little more potent. As a result, side effects like sleepiness can be more pronounced, so it’s usually not the first choice, says Dr. Mitrani.

On the positive side, newer versions of clonidine (Onyda XR) are available in liquid form, which makes it possible to control the dose to a finer degree. “With guanfacine, in its long-acting form, you’re working with 1 milligram, 2 milligrams, 3 milligrams, etcetera,” Dr. Mitrani explains. “With the liquid clonidine, you could do 0.15 milligrams or 0.25 milligrams. So, you can optimize the dose, and hopefully, reduce any negative side effects.”

Liquid clonidine, which, like guanfacine ER, lasts 24 hours, is also a good option for kids with sensory issues or an aversion to swallowing pills. Guanfacine ER tablets cannot be crushed or broken because then the medication may be released too quickly. Children must swallow time-release tablets whole.

Guanfacine and tic disorders

Guanfacine has been shown to be effective in treating some children with tic disorders. Researchers aren’t entirely sure why guanfacine can reduce tic severity, and their thinking has shifted in recent years. They theorize that the drug’s effects on the prefrontal cortex may help regulate attention and suppress tics.

Some studies show that the short-acting version of guanfacine, which kids typically take two to three times a day, can help manage tics better, says Dr. Mitrani. “Tics wax and wane; they come and go,” he explains. “They can be triggered by being excited, being tired, or being stressed.” Immediate-release guanfacine may be better-suited to address these fluctuations.

Kids with tic disorders often have other disorders, including ADHD. Studies show that guanfacine is more effective for kids with tics and ADHD than kids with tic disorders alone.

Guanfacine and autism

Guanfacine can also be prescribed off label to help treat autism. It may be effective in these cases because it helps regulate symptoms that are similar to or associated with ADHD, such as hyperactivity, impulsivity, and distractibility. (Researchers estimate that about one-third of children with autism also have ADHD.) Guanfacine is also sometimes used to address irritability, oppositional behavior, or problematic repetitive behaviors.

The post What Is Guanfacine? appeared first on Child Mind Institute.

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The association between cognitive disengagement syndrome and language in children with attention-deficit/hyperactivity disorder

AimThis study aims to explore the association between cognitive disengagement syndrome (CDS) and three aspects of language (narrative coherence, core language, and pragmatic language) in children with ADHD, and to examine whether these associations differ from those observed in neurotypical children.MethodsIn this cross-sectional study, parents completed questionnaires about their child’s CDS and pragmatic language, while children with ADHD (n = 45) and neurotypical children (n = 38), aged 7–11 years, completed tasks of narrative coherence and core language.ResultsCDS, after adjusting for age and sex, was significantly associated with pragmatic language in children with ADHD with a large effect (β = -0.51, p = .001), while CDS was significantly associated with core language in neurotypical children with a medium effect (β = -0.34, p = .04). There was a significant group difference in the association between CDS and pragmatic language (χ²(1) = 4.44, p = .04), with a stronger association in the ADHD group. After performing sensitivity analyses including inattention as an additional covariate, the associations ceased to be significant in both groups and there were no longer significant between-group differences.ConclusionThis study examined the association between CDS and language in children with and without ADHD. The findings suggest that there may be an association between CDS and pragmatic language in children with ADHD. However, sensitivity analyses including inattention as a covariate suggest that this association may largely reflect variance shared with inattention. Consequently, the association between CDS and language may partly reflect their shared association with ADHD symptoms. As this, to our knowledge, is the first study to investigate language in relation to CDS in children with ADHD, further research is warranted.
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X-Chromosome Gene Linked to Increased Autism Diagnosis in Males

Researchers at Baylor College of Medicine, the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital, and collaborating institutions have identified new genetic candidates that help explain why autism is diagnosed about four times more often in boys than it is in girls. The study, involving tests in induced pluripotent stem cell (iPSC)-derived neurons (iNeurons), revealed that small changes in the gene MECP2 on the X chromosome might help explain part of this difference.

Huda Zoghbi, MD, Distinguished Service Professor at Baylor, director of Duncan NRI, and a Howard Hughes Medical Institute investigator, is senior and corresponding author of the team’s published paper in The American Journal of Human Genetics, titled “A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism.” In their paper, the team concluded, “These findings suggest noncoding MECP2 variants can cause idiopathic, male-biased autism and provide a framework for uncovering regulatory variants in other X chromosome neurodevelopmental genes that may contribute to autism’s missing heritability.”

“Autism is a common, heritable neurodevelopmental trait that affects how a person communicates, interacts with others, and experiences the world, and is characterized by altered social interactions and restricted, repetitive behaviors or interests,” Zoghbi explained. “It is diagnosed about four times more in male individuals than in female individuals, suggesting sex-specific factors may increase male vulnerability,” the researchers added in their paper.

In the current study, the researchers drew from their long experience with gene MECP2, which is on the X chromosome and has been associated with neurodevelopmental conditions, including autism. “We tested the idea that the predominance of autism in males could be explained in part by mild mutations in an X chromosome gene’s regulatory regions,” commented Rebecca Meyer-Schuman, PhD, a postdoctoral associate in the Zoghbi lab. “Females might be protected from such a mild mutation because of their second X chromosome, but males, who have only one copy, would be more vulnerable. The regulatory regions are like dials that control whether a gene will be expressed and by how much. And what better place to start looking at these regulatory regions than the gene MECP2, where brain health depends on how much of the gene is expressed, and where mutations can cause neurodevelopmental disorders that include autism.”

Previous murine studies by Zoghbi lab and others have taught researchers that MECP2 produces a Goldilocks protein, meaning that it must maintain a “just right” concentration or activity level for a healthy brain. Having too little—about 50% or less of the normal levels—leads to Rett syndrome, and having twice the normal levels causes a different neurodevelopmental condition called MECP2 duplication syndrome. “Both loss-of-function and gain-of-function variants lead to severe neurodevelopmental conditions—Rett syndrome (MIM: 312750) and MECP2 duplication syndrome (MDS; MIM: 300260[intellectual developmental disorder, X-linked, syndromic, Lubs type (MRXSL)]), respectively,” the authors commented. “Because MECP2 is on the X chromosome, hemizygous male individuals have a more severe phenotype than heterozygous female carriers with the same variant.”

Meyer-Schuman also noted, “Previous studies in mice also showed us that milder changes in MECP2 levels, for instance reducing the expression by 30% or increasing it by 50%, do not cause the more severe features of Rett syndrome or MECP2 duplication syndrome like seizures or motor problems, but lead to autism-like behaviors.”

For their current study the team used a massively parallel reporter assay (MPRA) to screen the regulatory regions of the MECP2 gene in induced pluripotent stem-cell (iPC)-derived neurons. “This allowed us to identify and manipulate the regulatory regions and determine what kinds of changes would alter their function,” Meyer-Schuman said. The researchers also screened MECP2 regulatory regions in autistic individuals and tested the genetic variants they identified using the MPRA assays.

“We identified two regulatory regions where male autistic individuals inherited a variant from their unaffected mother that altered regulatory activity,” Meyer-Schuman said. “One of these variants reduced MECP2 expression by approximately 30% in human neurons, a magnitude that produces social deficits, hyperactivity and anxiety-like characteristics in mice. As predicted by the mouse model, this individual was diagnosed with autism and ADHD but had none of the defining characteristics of Rett syndrome.”

In their paper, the authors commented that their work supports a broader hypothesis that altered dosage or expression of sex chromosome genes are a major source of the male bias observed in autism. Zoghbi added, “These findings, a result of integrating human and animal studies, suggest that MECP2 regulatory variants can contribute to male-biased autism and reveal just the tip of the iceberg, providing a framework for uncovering regulatory variants in other X chromosome neurodevelopmental genes that may contribute to autism’s missing heritability.”

The post X-Chromosome Gene Linked to Increased Autism Diagnosis in Males appeared first on GEN – Genetic Engineering and Biotechnology News.

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The genetic orchestra of autism and its intersections with epilepsy, intellectual disability, and ADHD

Autism is a complex condition with marked phenotypic variability and a multifactorial etiology orchestrated by diverse genetic and environmental influences. In this review, we dissect what we refer to as autism’s “genetic orchestra”, spanning from the high-impact “soloists”, de novo and ultra-rare variants with large effect sizes, to the “polyphonic background” of common variants which individually exert modest effects but collectively have significant impact. We examine how this orchestra wires neural circuits, with convergent biological pathways modulating synaptic function and chromatin remodeling.

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Reliability of Childhood Autism Rating Scale, Second Edition, Assessments Using Telepsychiatry for Children With Neurodevelopmental Disorders and Their Caregivers: Randomized Feasibility Study

Background: The COVID-19 pandemic has increased the demand for telepsychiatry in neurodevelopmental assessment; however, few studies have examined the interrater reliability of clinician-rated autism scales, such as the Childhood Autism Rating Scale, Second Edition (CARS2), when used remotely. Although the feasibility and validity of telehealth assessments have been explored previously, the consistency between remote and in person CARS2 ratings by different clinicians remains underinvestigated. Objective: The objective of this study was to evaluate agreement between CARS2 total scores obtained by different evaluators using telepsychiatry and face-to-face assessments in children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD). Methods: In this randomized feasibility study, 75 children aged 6 to 17 years with diagnoses of ASD, ADHD, or both were enrolled at 5 medical institutions in Japan; 73 of 75 were included in the final analysis. Each participant underwent 2 independent CARS2 evaluations, one face-to-face and the other via telepsychiatry, conducted by different evaluators who were blinded to each other’s ratings. Remote assessments were conducted using a secure video platform with caregiver facilitation. Agreement was assessed using intraclass correlation coefficients (ICCs) for the overall sample and subgroups defined by primary diagnosis, sex, and age. Results: The overall ICC for CARS2 total scores between face-to-face and telepsychiatry assessments was 0.582 (95% CI 0.407‐0.717), indicating moderate agreement. The ICC was 0.546 among participants with ASD as the primary diagnosis and 0.495 among those with ADHD as the primary diagnosis. Point estimates were higher among girls than boys (0.666 vs 0.495) and among children aged 11 years or older than among those aged 10 years or younger (0.676 vs 0.419). In a sensitivity analysis including all participants with an ASD diagnosis, the ICC was 0.580. Conclusions: CARS2 total scores obtained through telepsychiatry showed moderate agreement with scores obtained through face-to-face assessment when the assessments were conducted by different evaluators in different settings. Higher point estimates were observed among older children and girls, although these subgroup findings should be interpreted cautiously. Telepsychiatry-based CARS2 assessment may be considered a complementary approach rather than a replacement for comprehensive face-to-face evaluation. Larger studies using more standardized assessment protocols are needed.
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Subject-independent classification of ADHD from pediatric EEG: a leakage-aware deep learning framework with interpretable neurophysiological mapping

BackgroundThe use of electroencephalography (EEG) in automated screening of Attention-Deficit/Hyperactivity Disorder (ADHD) has created a large body of literature that suggests promising outcomes, with reported classification accuracies often above 90%. A major methodological issue suggests that a substantial part of these results are actually due to data leakage, whereby EEG epochs pertaining to the same subject end up in both training and testing sets, allowing classifiers to capitalize on features specific to the individual rather than on genuine disorder-related biomarkers.MethodsWe assessed the performance of three classical machine learning algorithms, namely, Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM), as well as three deep learning models: Long Short-Term Memory (LSTM), Convolutional Neural Network (CNN), and CNN-BiLSTM, on a standard pediatric EEG dataset containing 121 children and 4,173 epochs. The performance of each model was compared in terms of both segment-wise cross-validation (Protocol A) and subject-wise cross-validation (without any data leakage, Protocol B).To evaluate neurotopographic plausibility without making unsupported causal assertions, we applied Deep SHapley Additive exPlanations (SHAP) to the best-generalizing architecture.ResultsThe performance discrepancy was substantial. Under segment-wise evaluation, the SVM operating on power spectral density (PSD) features reached 90.0% accuracy (95% CI: [89.1%, 90.9%], AUC = 0.96). However, the same model dropped to 65.6% (95% CI: [62.1%, 69.1%], AUC = 0.72) under subject-wise evaluation—a statistically significant 24.4 percentage point collapse (p < 0.001, Wilcoxon signed-rank). In contrast, deep architectures learning directly from raw EEG were resilient: the stand-alone CNN lost only 2.5 percentage points, achieving 72.7% accuracy (95% CI: [66.0%, 79.4%], AUC = 0.72, recall = 88.0%) on completely unseen participants. Post-hoc SHAP attribution identified the highest relative contributions in frontal (F3, Fz, F4) and central (Cz) electrodes, aligning with established ADHD neurophysiology.ConclusionHand-engineered spectral features are highly vulnerable to identity leakage, whereas end-to-end convolutional models generalize across subjects with realistic, uninflated performance. Strict subject-wise validation is strongly recommended as standard practice for translational EEG research.