Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Background And Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders.

Reprint of: Using a co-twin control design to evaluate alternative trait measures as indices of liability for substance use disorders.

To establish a trait-dispositional variable as an indicator of liability for the development of substance use disorders (SUDs), the trait must share heritable variance with SUDs and its association should not be primarily attributable to a direct impact of SUDs on characteristics that define the trait. The current work applied a co-twin control (CTC) modeling approach to data from two monozygotic twin samples to investigate the degree to which different measures of trait-impulsiveness represent indicants of vulnerability to SUDs (liability indicators), or outcomes or concomitants of SUDs (exposure indicators). The Five Factor Model (FFM) trait of conscientiousness was assessed via self-report, and a counterpart neurobehavioral trait of disinhibition was assessed both through self-report and using self-report and brain response measures combined.

Using a co-twin control design to evaluate alternative trait measures as indices of liability for substance use disorders.

To establish a trait-dispositional variable as an indicator of liability for the development of substance use disorders (SUDs), the trait must share heritable variance with SUDs and its association should not be primarily attributable to a direct impact of SUDs on characteristics that define the trait. The current work applied a co-twin control (CTC) modeling approach to data from two monozygotic twin samples to investigate the degree to which different measures of trait-impulsiveness represent indicants of vulnerability to SUDs (liability indicators), or outcomes or concomitants of SUDs (exposure indicators). The Five Factor Model (FFM) trait of conscientiousness was assessed via self-report, and a counterpart neurobehavioral trait of disinhibition was assessed both through self-report and using self-report and brain response measures combined.

Reduced premovement positivity during the stimulus-response interval precedes errors: Using single-trial and regression ERPs to understand performance deficits in ADHD.

Brain mechanisms linked to incorrect response selections made under time pressure during cognitive task performance are poorly understood, particularly in adolescents with attention-deficit hyperactivity disorder (ADHD). Using subject-specific multimodal imaging (electroencephalogram, magnetic resonance imaging, 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 amplitude features of source-resolved event-related potentials (ERPs) from brain-independent component processes within a critical (but often ignored) period in the action selection process, the stimulus-response interval, were associated with motor response errors (across trials) and error rates (across individuals).

Causal Network Modeling of the Determinants of Drinking Behavior in Comorbid Alcohol Use and Anxiety Disorder.

Background: Anxiety and depression disorders (internalizing psychopathology) occur in approximately 50% of patients with alcohol use disorder (AUD) and mark a 2-fold increase in the rate of relapse in the months following treatment. In a previous study using network modeling, we found that perceived stress and drinking to cope (DTC) with negative affect were central to maintaining network associations between internalizing psychopathology INTP and drinking in comorbid individuals. Here, we extend this approach to a causal framework.

Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.

Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.

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.

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 .

Does electroencephalogram phase variability account for reduced P3 brain potential in externalizing disorders?

Objective: Amplitude deficits of the P3 event-related potential (ERP) are associated with externalizing psychopathology but little is known about the nature of underlying brain electrical activity that accounts for this amplitude reduction. We sought to understand if group differences in task-induced phase-locking in electroencephalographic (EEG) delta and theta frequencies may account for P3-externalizing associations.

Methods: Adult males (N=410) completed a visual oddball task and frontal and parietal P3-related delta- and theta-band phase-invariant evoked energy and inter-trial phase-locking measures were investigated with respect to the externalizing spectrum, including substance dependence, adult antisociality, and childhood disruptive disorders.

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.

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.