Scott J. Burwell

Heritability and Molecular-Genetic Basis of Resting EEG Activity: A Genome-Wide Association Study

Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably.

The effects of recurrent episodes of depression on startle responses.

Prior work suggests that major depression is associated with abnormal startle blink responses; however, only chronic or recurrent depression appears to be associated with this effect. The current study tested this hypothesis directly by examining whether recurrent major depression accounted for the anomalous startle seen in major depression using a sample of 515 female twins from the Minnesota Twin Family Study. Blink responses recorded at the age of 20 were examined in relation to number of episodes of depression prospectively assessed from ages 11 to 20. Results showed that only subjects who had experienced multiple episodes of depression showed abnormal startle responses. Subjects who had experienced just one episode of depression in their lifetime did not differ from controls. This lends additional support to the idea that recurrent depression may have a different etiological basis than nonrecurrent depression.

Association between P3 event-related potential amplitude and externalizing disorders: A time-domain and time-frequency investigation of 29-year-old adults

This study determined whether time-domain P3 amplitude and time-frequency principal component (TF-PC) reductions are present in adulthood (age 29) when participants have largely passed through the age of heaviest substance misuse. Participants were assessed from age 17 through 29 for lifetime externalizing (EXT) disorders. EEG comparisons from three topographic regions were examined for P3 amplitude and TF-PCs at delta and theta frequency ranges. Significant P3 amplitude reductions were found in those with EXT for both regional and site-Pz analyses, with stronger effects observed the greater the EXT comorbidity. Reductions were also observed in all eight TF-PCs extracted, with a delta component yielding frontal effects not apparent in the time domain. Overall, results suggest that these brain measures continue, at age 29, to provide effective indices of EXT that potentially tap a neural substrate related to behavioral disinhibition.

One-year developmental stability and covariance among oddball, novelty, go/no-go, and flanker event-related potentials in adolescence: A monozygotic twin study

ERP measures may index genetic risk for psychopathology before disorder onset in adolescence, but little is known about their developmental rank-order stability during this period of significant brain maturation. We studied ERP stability in 48 pairs of identical twins (age 14-16 years) tested 1 year apart. Trial-averaged voltage waveforms were extracted from electroencephalographic recordings from oddball/novelty, go/no-go, and flanker tasks, and 16 amplitude measures were examined. Members of twin pairs were highly similar, whether based on ERP amplitude measures (intraclass correlation [ICC] median = .64, range = .44-.86) or three factor scores (all ICCs ≥ .69) derived from them. Stability was high overall, with 69% of the 16 individual measures generating stability coefficients exceeding .70 and all factor scores showing stability above .75. Measures from 10 difference waveforms calculated from paired conditions within tasks were also examined, and were associated with lower twin similarity (ICC median = .52, .38-.64) and developmental stability (only 30% exceeding .70). In a supplemental analysis, we found significant developmental stability for error-related negativity (range = .45-.55) and positivity (.56-.70) measures when average waveforms were based on one or more trials, and that these values were equivalent to those derived from averages using the current field recommendation, which requires six or more trials. Overall, we conclude that the studied brain measures are largely stable over 1 year of mid- to late adolescence, likely reflecting familial etiologic influences on brain functions pertaining to cognitive control and salience recognition.

Reduced Medial Frontal Positivity During the Stimulus-Response Interval Precedes Action Errors and Explains Task Deficits in Attention-Deficit Hyperactivity Disorder

Brain mechanisms responsible for errors during cognitive tasks are poorly understood, particularly in adolescents with attention-deficit hyperactivity disorder (ADHD). Using subject-specific multimodal imaging (EEG, MRI, behavior) during flanker task performance by a sample of 94 human adolescents (mean age = 15.5 years, 50% female) with varying degrees of ADHD symptomatology, we examined the degree to which amplitudes of source-resolved event-related potentials (ERPs) from brain independent components within a critical (but often ignored) period in the action selection process, the stimulus-response interval, predicted motor response errors (across trials) and error rates (across individuals). Reduced amplitudes of Frontocentral P3 (peaking at approximately 390 milliseconds in stimulus-locked ERPs) and Pre-Movement Positivity (PMP, peaking at approximately 110 milliseconds pre-response in response-locked ERPs) in projections from posterior medial frontal cortex (pMFC) predicted erroneous responses, and reduced amplitude of PMP predicted a larger participant error rate. After regressing stimulus-from response-locked ERPs, we concluded that errors primarily depended upon response selection processes reflected in PMP amplitude. Finally, mediation analyses showed that smaller PMPs on correct response trials was associated with the higher frequency of errors committed by adolescents with more ADHD symptoms. These results bolster the importance of pMFC in action selection and support the possible value of using PMP as an intervention target to remediate performance deficits in ADHD.

Heritability and molecular-genetic basis of resting EEG activity: A genome-wide association study: Genome-wide association study of resting EEG

Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably.

Heritability and molecular-genetic basis of resting EEG activity

Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably.