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Association Between Smoking, Brain Activity, Genes, and ADHD

Smoking, Neurocircuitry and Genes in Adult ADHD

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT00915798
Enrollment
89
Registered
2009-06-08
Start date
2009-07-31
Completion date
2016-06-30
Last updated
2017-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Smoking, Withdrawal Nicotine, ADHD

Brief summary

The study investigated the underlying mechanisms of smoking in young adults by examining the associations between smoking, brain activity, dopamine genes, and attention deficit hyperactivity disorder (ADHD).

Detailed description

The study investigated the underlying mechanisms of smoking in young adults by examining the associations between smoking, brain activity, dopamine genes, and attention deficit hyperactivity disorder (ADHD). Four groups of young adults were recruited: (1) smokers with ADHD; (2) nonsmokers with ADHD; (3) normative control smokers; and (4) normative control nonsmokers. Smoking was assessed via questionnaires and salivary cotinine levels. Brain activity was examined via functional Magnetic Resonance Imaging (fMRI). Each nonsmoker underwent an fMRI scan during an experimental task consisting of mathematical problems. Smokers underwent two fMRI scans during similar experimental tasks under the following two conditions: (1) after smoking a cigarette and (2) after overnight abstinence. The association between the DRD4-7 repeat allele and smoking was explored.

Interventions

BEHAVIORALCigarette smoking

Participants had an fMRI scan during an experimental task consisting of mathematical problems after smoking a cigarette.

BEHAVIORALAbstinence

Participants had an fMRI scan during an experimental task consisting of mathematical problems after smoking abstinence.

Sponsors

National Institute on Drug Abuse (NIDA)
CollaboratorNIH
University of California, Irvine
Lead SponsorOTHER

Eligibility

Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

1. Smokers with ADHD * Cigarette smoking for the last year * ADHD diagnosis 2. Nonsmokers with ADHD * No history of regularly smoking cigarettes * ADHD diagnosis 3. Normative control smokers * Cigarette smoking for the last year * No history and diagnosis of ADHD 4. Normative control nonsmokers * No history of regularly smoking cigarettes * No history and diagnosis of ADHD

Exclusion criteria

* Children under the age of 18 * Adults above the age of 45 * Pregnancy or planning to become pregnant * Any major medical illness * Any mental disorders that require medication (except stimulant medication) * Any contraindications to fMRI scanning * Not speaking English

Design outcomes

Primary

MeasureTime frameDescription
Brain ActivityOne MRI session for nonsmokers and two MRI sessions for smokersBOLD z-score of smokers with ADHD after abstinence/smoking a cigarette, control smokers after abstinence/smoking a cigarette, nonsmokers with ADHD, and control nonsmokers. All participants performed a mathematical task in the MRI scanner. Higher BOLD z-scores indicate greater brain activation.

Secondary

MeasureTime frameDescription
DRD4 Genotypeone time blood draw
Salivary CotinineOnce per week for 4 weeksAverage level of salivary cotinine over all time points (microgram/milliliter)

Countries

United States

Participant flow

Recruitment details

Smokers and nonsmokers with and without ADHD

Participants by arm

ArmCount
ADHD Smokers
ADHD smokers participated in two conditions: (1) after smoking a cigarette and (2) after overnight abstinence.
19
ADHD Nonsmokers
ADHD nonsmokers participated in the abstinence condition.
21
Control Smokers
Control smokers participated in two conditions: (1) after smoking a cigarette and (2) after overnight abstinence.
23
Control Nonsmokers
Control nonsmokers participated in the abstinence condition.
26
Total89

Baseline characteristics

CharacteristicADHD SmokersADHD NonsmokersControl SmokersControl NonsmokersTotal
Age, Continuous23.00 years
STANDARD_DEVIATION 1.7
27.24 years
STANDARD_DEVIATION 7.96
25.04 years
STANDARD_DEVIATION 4.29
22.69 years
STANDARD_DEVIATION 1.85
24.44 years
STANDARD_DEVIATION 4.88
Gender
Female
2 Participants6 Participants4 Participants18 Participants30 Participants
Gender
Male
17 Participants15 Participants19 Participants8 Participants59 Participants
Region of Enrollment
United States
19 Participants21 Participants23 Participants26 Participants89 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
0 / 190 / 210 / 230 / 26
serious
Total, serious adverse events
0 / 190 / 210 / 230 / 26

Outcome results

Primary

Brain Activity

BOLD z-score of smokers with ADHD after abstinence/smoking a cigarette, control smokers after abstinence/smoking a cigarette, nonsmokers with ADHD, and control nonsmokers. All participants performed a mathematical task in the MRI scanner. Higher BOLD z-scores indicate greater brain activation.

Time frame: One MRI session for nonsmokers and two MRI sessions for smokers

Population: Discrepancies between participant flow and number of participants analyzed are due to motion artifacts, which compromised the MRI findings. Thus, a number of participants had to be excluded from the MRI data analysis.

ArmMeasureGroupValue (MEAN)Dispersion
Smokers With ADHD After AbstinenceBrain ActivityBOLD Frontal Lobe2.08 z-scoreStandard Deviation 0.23
Smokers With ADHD After AbstinenceBrain ActivityBOLD Parietal Lobe2.69 z-scoreStandard Deviation 0.53
Smokers With ADHD After AbstinenceBrain ActivityBOLD Occipital Lobe2.72 z-scoreStandard Deviation 0.47
Nonsmokers With ADHDBrain ActivityBOLD Frontal Lobe2.01 z-scoreStandard Deviation 0.63
Nonsmokers With ADHDBrain ActivityBOLD Parietal Lobe2.30 z-scoreStandard Deviation 0.37
Nonsmokers With ADHDBrain ActivityBOLD Occipital Lobe2.87 z-scoreStandard Deviation 0.74
Control Smokers After AbstinenceBrain ActivityBOLD Occipital Lobe2.71 z-scoreStandard Deviation 0.61
Control Smokers After AbstinenceBrain ActivityBOLD Frontal Lobe2.24 z-scoreStandard Deviation 0.18
Control Smokers After AbstinenceBrain ActivityBOLD Parietal Lobe2.48 z-scoreStandard Deviation 0.37
Control NonsmokersBrain ActivityBOLD Parietal Lobe2.77 z-scoreStandard Deviation 0.71
Control NonsmokersBrain ActivityBOLD Frontal Lobe2.30 z-scoreStandard Deviation 0.2
Control NonsmokersBrain ActivityBOLD Occipital Lobe2.88 z-scoreStandard Deviation 0.49
Smokers With ADHD After SmokingBrain ActivityBOLD Frontal Lobe2.19 z-scoreStandard Deviation 0.25
Smokers With ADHD After SmokingBrain ActivityBOLD Parietal Lobe2.61 z-scoreStandard Deviation 0.72
Smokers With ADHD After SmokingBrain ActivityBOLD Occipital Lobe2.80 z-scoreStandard Deviation 0.75
Control Smokers After SmokingBrain ActivityBOLD Parietal Lobe2.60 z-scoreStandard Deviation 0.7
Control Smokers After SmokingBrain ActivityBOLD Occipital Lobe2.90 z-scoreStandard Deviation 0.8
Control Smokers After SmokingBrain ActivityBOLD Frontal Lobe2.26 z-scoreStandard Deviation 0.23
Comparison: Frontal BOLD during abstinence in smokers and nonsmokersp-value: 0.46ANOVA
Comparison: Parietal BOLD during abstinence in smokers and nonsmokersp-value: 0.012ANOVA
Comparison: Occipital BOLD during abstinence in smokers and nonsmokers.p-value: 0.04ANOVA
Comparison: Frontal BOLD smoking versus nonsmoking in smokers with ADHD compared to control smokers.p-value: 0.22ANOVA
Comparison: Parietal BOLD smoking versus nonsmoking in smokers with ADHD compared to control smokers.p-value: 0.51ANOVA
Comparison: Occipital BOLD smoking versus nonsmoking in smokers with ADHD compared to control smokers.p-value: 0.69ANOVA
Secondary

DRD4 Genotype

Time frame: one time blood draw

Population: Discrepancies between participant flow and data analyze reflect that not all participants provided blood samples. Dopamine genotypes were only available for participants who were also enrolled in the Multimodal Treatment for ADHD Study (MTA-Study).

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-4R/7R1 Participants
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-4R/4R5 Participants
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-3R/4R1 Participants
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-3R/3R1 Participants
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-2R/4R2 Participants
Smokers With ADHD After AbstinenceDRD4 GenotypeDRD4-2R/2R0 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-2R/2R1 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-3R/3R0 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-4R/7R5 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-3R/4R0 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-4R/4R1 Participants
Nonsmokers With ADHDDRD4 GenotypeDRD4-2R/4R0 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-4R/4R3 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-3R/4R0 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-3R/3R0 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-2R/2R0 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-2R/4R0 Participants
Control Smokers After AbstinenceDRD4 GenotypeDRD4-4R/7R2 Participants
Control NonsmokersDRD4 GenotypeDRD4-2R/4R1 Participants
Control NonsmokersDRD4 GenotypeDRD4-2R/2R0 Participants
Control NonsmokersDRD4 GenotypeDRD4-4R/4R7 Participants
Control NonsmokersDRD4 GenotypeDRD4-3R/3R0 Participants
Control NonsmokersDRD4 GenotypeDRD4-4R/7R10 Participants
Control NonsmokersDRD4 GenotypeDRD4-3R/4R0 Participants
Secondary

Salivary Cotinine

Average level of salivary cotinine over all time points (microgram/milliliter)

Time frame: Once per week for 4 weeks

Population: Discrepancies between participants cotinine samples and participant flow are due to the fact that not all participants provided useful saliva samples.

ArmMeasureValue (MEAN)Dispersion
Smokers With ADHD After AbstinenceSalivary Cotinine100.06 Microgram/milliliterStandard Deviation 111.52
Nonsmokers With ADHDSalivary Cotinine24.53 Microgram/milliliterStandard Deviation 86.66
Control Smokers After AbstinenceSalivary Cotinine104.99 Microgram/milliliterStandard Deviation 84.75
Control NonsmokersSalivary Cotinine23.13 Microgram/milliliterStandard Deviation 52.65

Source: ClinicalTrials.gov · Data processed: Feb 21, 2026