Determining the Impact of Air Pollution on the Developing Brain

Study Overview
=================
Brief Summary
-----------------
Background: Recent studies have linked exposure to airborne particulate matter (PM) to neurodevelopmental outcomes but the findings are mixed and mechanisms are unclear. We aim to determine the impact of PM on the developing brain of schoolchildren in Poland, a European country characterized by very high levels of air pollution. The investigators aim to determine the impact of PM on the developing brain of schoolchildren in Poland, a European country characterized by very high levels of air pollution. Study area: 19 towns in three voivodeships (Lesser Poland, Silesian, Opole) in the southern Poland. To reduce confounding by urbanicity and at the same time, to achieve sufficient contrasts in PM levels without too high logistic costs, towns were selected by size (big and small) and by PM levels (high, medium and low). Design: Case-control study with 800 children recruited over two school years, with two population controls per one ADHD case. Suspected cases will be recruited in specialized facilities and presumably ADHD-free children will be recruited in primary schools. Exposure assessment: Poland-wide PM and other air pollutants' grids will be created for the years 2006 to 2021 using statistical models to incorporate land use data, estimates from transport models, satellite observations and air pollution measurements from Polish monitoring network. Prenatal, early-life, lifelong and concurrent exposures will be calculated. Psychological testing: Every child and their parents will complete a series of psychological tests and interviews that will be conducted during their three visits to the recruitment facility. Neuroimaging: Each participant will undergo a Magnetic Resonance Imaging (MRI) scanning session that will be performed accordingly to the Human Connectome Adolescent Brain Cognitive Development project recommendations. Scanning will be performed on a single scanner in Krakow.

Official Title
-----------------
NeuroSmog: Determining the Impact of Air Pollution on the Developing Brain

Conditions
-----------------
Attention Deficit Hyperactivity Disorder, Attention, Executive Functioning, Social Functioning

Intervention / Treatment
-----------------
* Diagnostic Test: Psychological testing and MRI imaging


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Attending school in one of the specified towns Age 10-13 years (4th-6th grade) Native Polish speaker Normal or above intelligence Standard educational opportunities Normal or corrected to normal visual and auditory acuity No gross sensory deficit, no gross behavioural problems No history of neurological disease Exclusion Criteria: Autism spectrum disorder (ASD) FAS FAE Intellectual disability Metabolic disorders Genetic disorders Epilepsy Cerebral palsy Mood disorders Tourette Syndrome Other illnesses including pharmacotherapy Apgar score < 8 Low birth weight (below 2500 g) Preterm birth (below 35th weeks of gestation)

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 13 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with Attention Deficit Hyperactivity Disorder<br>Cases | Diagnostic Test: Psychological testing and MRI imaging<br>* Every child will have three sessions with psychologists and be diagnosed as having or not having ADHD. Every child will be invited to Krakow to undergo MRI measurements, including resting-state and event-related functional MRI, Diffusion Tensor Imaging (DTI), and T1/T2 structural MRI.<br>|
| Children without Attention Deficit Hyperactivity Disorder<br>Population controls | Diagnostic Test: Psychological testing and MRI imaging<br>* Every child will have three sessions with psychologists and be diagnosed as having or not having ADHD. Every child will be invited to Krakow to undergo MRI measurements, including resting-state and event-related functional MRI, Diffusion Tensor Imaging (DTI), and T1/T2 structural MRI.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention Deficit Hyperactivity Disorder (ADHD) | ADHD and comorbidities will be assessed by Conners 3 questionnaire | October 1, 2020 until December 31, 2022 | 
| Cognitive functioning | Memory, attention, and executive functions measurement will be assessed by Diagnostic battery for cognitive functions evaluation (PU1) | October 1, 2020 until December 31, 2022 | 
| Attention control | Attention Network Test (ANT) will be used. | October 1, 2020 until December 31, 2022 | 
| Sustained and selective attention | Computer Conners Continuous Performance Task (CPT) will be used. | October 1, 2020 until December 31, 2022 | 
| Inhibition control | Conditioned Approach Response Inhibition Task (CARIT) will be used as part of MRI measurements. | October 1, 2020 until December 31, 2022 | 
| Inhibition control | Go/No Go task will be used as part of MRI measurements. | October 1, 2020 until December 31, 2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Full-Scale Intelligence Quotient (IQ) | IQ will be measured by Stanford-Binet Intelligence Scales, 5th Edition (SB5). | October 1, 2020 until December 31, 2022 | 
| Family functioning | Polish adaptation of the FACES-IV (Flexibility and Cohesion Evaluation Scales; SOR) will be used to estimate social functioning of the children (family functioning). | October 1, 2020 until December 31, 2022 | 
| Relationships with siblings | Siblings Relationship Questionnaire (KRR), which is a supplement for the SOR Scale will be used to assess social functioning of the children (relationships with siblings). | October 1, 2020 until December 31, 2022 | 
| Behavioural, emotional, and social problems | Youth Self-Report Scale (YSR) will be used for this assessment. | October 1, 2020 until December 31, 2022 | 
| Behavioural problems | Child Behaviour Checklist (CBCL) questionnaire will collect information on the eight syndrome domains: anxious/depressed, depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behaviour, aggressive behaviour | October 1, 2020 until December 31, 2022 |