Researchers found a way to use brain scans to spot which kids are at risk for depression – anxiety and attention problems

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Children’s mental health issues are hard to predict until they’re causing problems, but researchers may have found a way to use brain scans to spot which kids are at risk for depression, anxiety and attention problems.

“We’re facing a tremendous epidemic with teen anxiety and depression, and we wanted to find an early marker that predicted the development of anxiety, depression and attentional symptoms,” said the study’s lead author, Susan Whitfield-Gabrieli. She’s a professor of psychology and director of the Northeastern University Biomedical Imaging Center, in Boston.

In a small sample of less than 100 children without known mental health concerns, the research team found that connections in certain areas of the brain seen at age 7 could help predict mental health concerns that developed four years later.

“The study could have great clinical implications,” Whitfield-Gabrieli said. “Identification of these biomarkers at such a young age could promote early interventions – exercise, mindfulness, cognitive behavioral therapy – which might mitigate symptoms and possibly even prevent the progression of psychiatric illness.”

But she was also quick to note that this is an early study, and scans aren’t available as a screening tool now. “Although I think that neuroimaging may become a useful screening tool in the future, I don’t think that we are there yet,” Whitfield-Gabrieli said.

Dr. Victor Fornari, vice chairman of child and adolescent psychiatry at the Zucker Hillside Hospital in Glen Oaks, N.Y., reviewed the findings.

“The identification of biomarkers for psychiatric disorders remains a promising area of research investigation,” he said, adding that this study showed it might be possible to visualize and measure mental health vulnerabilities before they cause symptoms.

The study included 94 children who began the study at age 7 (including 53 boys and 41 girls). Most (77) had no known mental health concerns; 17 were at risk of a reading problem.

The kids all had functional MRI scans. This type of scan gives more detail about what’s going on in the brain by measuring changes in blood flow, according to the Radiological Society of North America.

The investigators found that a certain pattern of connections in one area of the brain at age 7 could help predict who might have depression and anxiety by age 11.

They also found that weaker connections in this brain area forecast who might have fewer attention problems at age 11.

Whitfield-Gabrieli said she hopes to look at brain scans in infants next, to see if these mental health concerns could be identified even earlier in life.

If further studies confirm that researchers can predict who’s at risk for conditions such as depression or attention-deficit/hyperactivity disorder, interventions such as cognitive behavioral therapy or mindfulness training might help.

Whitfield-Gabrieli said the good news is that “behavioral interventions don’t have side effects.”

The findings were published online Dec. 26 in JAMA Psychiatry.


Individuals with an intellectual disability have neurodevelopmental deficits characterized by limitations in intellectual functioning and adaptive behavior. These disabilities originate and manifest before the age of 18 and can be associated with a considerable number of related and co-occurring problems including mental health (e.g., depression, and anxiety), neurodevelopmental (e.g., autism spectrum disorders, and attention deficit hyperactivity disorder), as well as neurological (e.g., infantile cerebral palsy) and medical conditions (e.g., meningitis).  

Intellectual functioning 

Intellectual functioning is generally called intelligence and includes a wide range of mental activities such as the ability of logical reasoning and practical intelligence (problem-solving), ability in learning, verbal skills, and so on.

It manifests and expresses itself through a numerous set of capabilities, behaviors, thoughts, and emotions. In other words, intellectual functioning is definable as the global ability that allows the individual to understand reality and interact with it.

Intellectual functioning is commonly measured by the intelligence quotient (IQ), which represents a total score obtained from standardized tests (IQ tests) developed for evaluating human intelligence. IQ test score has a median of 100 and a standard deviation of 15. A score of 70 or below (two standard deviations below the median) indicates intellectual limitations. 

Adaptive behavior

These disabilities express as lacking competence in social, conceptual, and practical skills. Social skills include interpersonal skills, social responsibility, self-esteem, gullibility, naivety, resolution of social problems, and the ability to follow the rules of the society and to obey the laws.

Conceptual skills include the ability to understand time, finance, and language. Practical skills include the ability to use tools, carry out activities of daily living, and interact with other people.

All these skills are learned throughout development and performed in response to common problems and simple/complex tasks as well as expectations from our community and society. Obviously, these behavioral responses become progressively more complex with age. Several validated tools are useful for assessing limitations in adaptive behavior.

Etiology

While many causes of intellectual disability are not known, the etiology of intellectual disability mainly divides into genetic abnormalities and environmental exposure. Genetic abnormality can be a single gene mutation, copy number variation, or chromosomal abnormality that causes an inborn error of metabolism, neurodevelopmental defect, and neurodegeneration. Environment exposure can be maternal exposure to toxin/infectious agents, uncontrolled maternal medical conditions, delivery complications, and post-natal trauma and exposure to toxin/infectious agents. The most common known preventable or environmental cause of intellectual disability is fetal alcohol syndrome, the most common chromosomal cause is Down syndrome, and the most common genetic cause is Fragile X syndrome. 

Genetic

The genetic abnormality may cause an inborn error of metabolism neurodevelopmental defect, or neurodegeneration. An inborn error of metabolism, toxic by-products accumulate, causing intellectual disability and other behavioral problems. Phenylketonuria (PKU) is one of the inborn errors of metabolism that occurs in approximately 0.01% of the newborn. PKU most commonly results from phenylalanine hydroxylase defect inherited in an autosomal recessive fashion. The defect disables the liver from converting phenylalanine to para-tyrosine. The consequent accumulation of phenylalanine is the culprit of intellectual disability. Neurological damage from PKU is irreversible but preventable. Therefore, newborn screening of PKU is mandatory in the U.S. and other countries. Early screening followed by prompt initiation of a low phenylalanine diet before the age of 3 may prevent intellectual disability.[1] Recently, different rare types of hyperphenylalaninemia were described, including the deficiency of the enzyme dihydropyridine reductase and a deficiency of a cofactor, biopterin.[2]

Lesch-Nyhan syndrome is an X-linked inborn error of metabolism caused by purine metabolism enzyme deficiency. This condition results from a mutation in HGPRT.[3] This mutation leads to a buildup of uric acid, which causes severe self-mutilating behavior of biting mouth and finger as well as intellectual disability.[4] Other known inborn errors of metabolism that result in intellectual disability are Niemann-Pick disease, Hunter disease, Hurler disease, maple syrup urine disease, Hartnup disease, homocystinuria, and galactosemia.

A neurodevelopmental defect presents in Fragile X syndrome, a leading genetic cause of intellectual disability. It results from a single gene mutation in FMR1 (Xq27.3) gene. In most cases, CGG repeat of the FMR1 gene expands to over 200 times. The expansion leads to a phosphorylated CG pattern, causing methylation imprinting of the gene, thereby silencing FMR1 gene expression. FMR1 is a transcription factor of hundreds of genes expressed in the central nervous system, and its disruption causes intellectual disability as well as behavioral disturbance, and seizure.[5] Neurodevelopment defect also presents in neurofibromatosis type 1, also known as von Recklinghausen syndrome, an autosomal dominant condition, caused by mutations of NF1. Its characteristic presentation is abnormal neural cell migration leading to cafe au lait spot, movement disorder, and intellectual disability.[6]

Neurodegeneration leading to intellectual disability presents in Rett syndrome (RS), an X-linked dominant degenerative condition only seen in female secondary to mutation of the MeCP2 gene. In patients with RS, cerebral atrophy occurs at substantia nigra, causing defects in the dopaminergic nigrostriatal pathway, starting at 6 to 18 months of age.[7]

IQ alterations can also occur as part of a clinical picture in other genetic syndromes. In many cases, the intellectual deficit appears to be limited and can occur at different stages of neurodevelopment, also in terms of cognitive decline. For example, in chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, which is one of the most common multiple anomaly syndromes in humans, it is usually described a cognitive decline rather than an early onset intellectual disability.[8]

Environmental

Environmental exposure during pregnancy may lead to intellectual disability, which can be caused by maternal exposure to a toxin, infectious agent, uncontrolled maternal condition, and birth complications.

One common toxic substance that leads to an intellectual disability during pregnancy includes alcohol. Alcohol exposure, indeed, commonly causes intellectual disability along with other developmental abnormalities, in a condition known as fetal alcohol syndrome.[9] Fetal exposure to alcohol inhibits the production of retinoic acid, which is an essential signaling molecule for the development of the nervous system. Even a small amount of alcohol at any trimester of pregnancy may cause fetal alcohol syndrome.[10]. Exposure to opioids, cocaine, and teratogenic medications may also lead to intellectual disability.

Common, well-known infectious agent that causes intellectual disability are rubella and HIV. Maternal rubella infection in the initial trimester of pregnancy leads to intellectual disability approximately 10 to 15% of the time; it can rise to above 50% with infection during the first month. Immunization may prevent the mother from rubella infection.[11] HIV may be transferred vertically from mother to infant. Infants with HIV may develop encephalopathy, seizures, and intellectual disability within the first year of life secondary to microcephaly, immunosuppression, and Pneumocystis jiroveci pneumonitis (PCP) infection.[12] Excessive neuro-inflammation causes overstimulation of the N-methyl-D-aspartate type receptor (NMDAR) system that leads to neuronal injury. Antiretroviral therapy to mother and prophylactic treatment with zidovudine to newborn exposed to HIV has significantly reduced the transmission.[12] Other known infectious exposures to mothers that may cause intellectual disability of the newborn are cytomegalic inclusion disease, syphilis, and toxoplasmosis.

Uncontrolled maternal medical conditions may lead to intellectual disability. Pregnancy hypertension, asthma, urinary tract infection, pre-pregnancy obesity, and pre-gestational diabetes were shown to increase the risk significantly.[13] Furthermore, uncontrolled maternal diabetes, malnutrition, and obstetrical complications causing anoxia (placenta previa, placenta abruption, and umbilical cord prolapse) may also cause intellectual disability.[14]

An intellectual disability is acquirable during early childhood. Causes include infection (notably encephalitis and meningitis), head trauma, asphyxia, intracranial tumor (either directly or indirectly through seizure, surgery, and chemotherapy), malnutrition, and exposure to toxic substances.[15]

Epidemiology

The prevalence of intellectual disability in developing countries is estimated to range from 10 to 15 per 1000 children of those about 85% have a mild intellectual disability. From 1 to 3% of the Western population is estimated to have an intellectual disability. Incidence is challenging to accurately calculate as mild disabilities may be under-recognized until later in childhood. The intellectual disability is reported to peak at the ages of 10 to 14 years and is 1.5 times more prevalent in males than females.[16]

History and Physical

Keeping up with daily functions is often challenging for individuals with a different degree of intellectual disability. They may have difficulty feeding themselves, going to the bathroom, and dressing. They also may have difficulty getting along with their family and friends because of a problem with communication as well as poor impulse control. They may have trouble excelling academically and socially at school.

Concerning clinical history, symptoms of intellectual disability usually begin during childhood or adolescence. Moreover, delays in language or motor skills may be observed by age two. Nevertheless, a significant number of children with mild levels of intellectual disability may not get identified until school-age.

A comprehensive history of patients with intellectual disability must include the following:

  • Information about the mother’s pregnancy, labor, and delivery
  • Mother’s use of substance or medications during pregnancy
  • Mother suffered any uncontrolled medical condition
  • Was delivery pre-term?
  • Was there any issue with delivery?
  • Patient’s sensory, social, language, and motor developments to detect any developmental delay
  • Patient’s exposure to infection, trauma, and toxin
  • Patient’s medical conditions
  • Patient’s psychiatric conditions
  • Medications that the patient is taking
  • Patient’s family history of psychiatric and medical conditions
  • Patient’s living situation, caretaker
  • Patient’s behavior toward caretaker, parents, and siblings
  • Patient’s academic performance at school
  • Patient’s behavioral disturbance reported at school

Physical examination is vital to differentiate intellectual disorders from other conditions. A full neurological exam should be performed to identify any deficit that may mimic intellectual disability and comorbid symptoms. Visual and hearing tests are particularly important as abnormal vision or hearing causes difficulty with communication, leading to delay in developing language and social skills, closely mimicking intellectual disability. Motor dysfunctions such as spasticity, hypotonia, hyperreflexia, and involuntary movements commonly present in individuals with intellectual disabilities.[17] 

Some physical characteristics are closely associated with a specific diagnosis as following:

  • Down syndrome: slanted eyes, flat nasal bridge, protruding tongue, small chin, and single crease palm
  • Fragile X syndrome: long and narrow face, prominent forehead and jaw, large ears, and large testicles in male
  • Fetal alcohol syndrome: smooth philtrum, thin vermilion, and small palpebral fissures
  • Prader-Willi: obesity secondary to compulsive eating behavior, hypogonadism, small hands, and feet
  • Cat’s cry (Cri-du-chat) syndrome: microcephaly, hypertelorism, low-set ears, and micrognathia
  • Phenylketonuria: bizarre movements such as twisting hand mannerisms, poor motor coordination, and perceptual difficulties

Evaluation

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of intellectual disability requires deficits in intellectual function, deficits in adaptive function, and onset before the age of 18. The IQ test is widely used to assess the intellectual function of individuals. IQ test derives from Stanford-Binet Intelligence Scales, used for school placement in France. Lewis Terman adapted the test to measure general intelligence. Scores were reported as “mental age” divided by chronological age, multiplied by 100. The current version of the IQ test is standardized, and two standard deviations below the test taker’s group calculate as IQ of 70. An IQ of 70 or below suggests intellectual disability diagnosis. Based on the IQ score, the severity grading appears below.

  • IQ 50 to 70: mild intellectual disability (85% of cases)
  • IQ 35 to 50: moderate intellectual disability (10% of cases)
  • IQ 20 to 35: severe intellectual disability (4% of cases)
  • IQ below 20: Profound intellectual disability (1% of cases)

However, it is no longer a standard to classify intellectual disability by IQ score alone. For instance, if an individual has IQ below 70, but has a good adaptive function, the subject does not have an intellectual disability. On the other side, individuals with a normal, or even higher than normal IQ, may manifest severe deficits in adaptive functions and are, therefore, classified as having an intellectual disability. In turn, the current diagnosis of intellectual disability also considers a person’s adaptive function.[18] The Adaptive Behaviour Assessment System can measure adaptive function.[19] It encompasses the social and practical domain. Adaptive function measures ability in communication, social participation, and independent living.

The DSM-5 also has “Unspecified Intellectual Disability” (Intellectual Developmental Disorder) to describe individuals over the age of 5 suspected of having an intellectual disability who has difficulty completing required tests, usually because of limitations resulting from blindness, deafness, or concurrent mental illness.

Chromosomal analysis, urine and blood tests, and neuroimaging techniques have been used to elucidate the etiology of intellectual disability.

Traditionally, chromosomal analysis has been done by parents’ choice before the birth of a child via amniocentesis (performed at 15 weeks of gestation) or chorionic villi sampling (8 to 10 weeks of gestation). It is a highly specific test for Down syndrome, and early detection of chromosomal abnormalities allow a decision to terminate the pregnancy. Recently, a cell-free fetal DNA test has appeared as a noninvasive prenatal test for Down syndrome. It has demonstrated a higher detection rate, positive predictive value, and false-positive rate.[20] Another current technique of chromosomal analysis is fluorescent in situ hybridization (FISH), which is useful to identify the microscopic deletion of the chromosome.[21]

Urine and blood analysis allow the evaluation of enzyme activities and detection of inborn errors of metabolism, including PKU, Lesch-Nyhan syndrome, galactosemia, and Hurler syndrome with the help of advanced techniques such as tandem mass spectroscopy and gas chromatography.[22]

As for neuroimaging techniques, computerized tomography (CT) or magnetic resonance imaging (MRI) has been useful to identify microcephaly, cerebral developmental delay, and cerebral palsy.[23] Functional MRI and diffusion tensor imaging are being researched to identify abnormalities in neural circuit pathways. For example, Fragile X syndrome with aberrant frontal-striatal pathways has been found associated with ADHD symptoms. Electroencephalography (EEG) is used to detect seizures that often accompany intellectual disability; though findings do not direct to specific diagnoses.[24]


More information: Learn more about promoting good mental health in children from Mental Health America.

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