The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India.

The global burden of disease attributable to externalizing disorders such as alcohol misuse calls urgently for effective prevention and intervention. As our current knowledge is mainly derived from high-income countries such in Europe and North-America, it is difficult to address the wider socio-cultural, psychosocial context, and genetic factors in which risk and resilience are embedded in low- and medium-income countries. c-VEDA was established as the first and largest India-based multi-site cohort investigating the vulnerabilities for the development of externalizing disorders, addictions, and other mental health problems. Using a harmonised data collection plan coordinated with multiple cohorts in China, USA, and Europe, baseline data were collected from seven study sites between November 2016 and May 2019. Nine thousand and ten participants between the ages of 6 and 23 were assessed during this time, amongst which 1278 participants underwent more intensive assessments including MRI scans. Both waves of follow-ups have started according to the accelerated cohort structure with planned missingness design. Here, we present descriptive statistics on several key domains of assessments, and the full baseline dataset will be made accessible for researchers outside the consortium in September 2019. More details can be found on our website [cveda.org].

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol.

BACKGROUND: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. METHODS: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. DISCUSSION: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.

Discrete time survival analysis was used to assess the age-specific association of event-related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens.

How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity.

CONTEXT: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. OBJECTIVE: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. DESIGN, SETTING, AND PARTICIPANTS: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12-26; N = 2,128). MAIN OUTCOME MEASURES: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. RESULTS: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. CONCLUSIONS: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.

A Review of Historical Context and Current Research on Cannabis Use in India.

Background: The cultivation and use of cannabis is historically rooted in the Indian subcontinent and this rich heritage of cannabis use dates back to at least two thousand years. Cannabis remains an illicit substance in India despite its changing status globally with many countries legalizing cannabis use in recent years. Scientific research on cannabis use in India has also been sparse. Method: Extensive search of online databases resulted in the identification of 29 original research studies pertaining to one of three areas of cannabis research; a) prevalence of cannabis use b) psychological correlates of cannabis use, c) cannabis use in substance use treatment settings. Findings: We found that most Indian studies used very basic quantitative research designs and had poor scientific rigor. Samples were small, region specific and included only males. Data analyses were limited to descriptive methods. The criteria for cannabis use in most of the reviewed studies were not rigorous and prone to biases. Conclusion & Implications: With changing attitudes and loosening of restrictions on cannabis use, the prevalence of new users is rising dramatically particularly in the college going population. This presents a strong need for research on motivations and attitudes to cannabis use and how those can influence patterns of use, and also the short- and long-term effects of use. More studies with stronger research designs (both cross sectional and longitudinal) are required for the study of cannabis use and this knowledge will be critical for managing the growing substance epidemic, generating public health solutions as well as formulating effective policy frameworks.

Prospective memory in early and established psychosis: An Indian perspective.

Individuals affected by psychosis often have deficits in several neurocognitive functions. Prospective memory (PM), the ability to remember to do things, is crucial for activities of daily living, social and occupational functioning, but very few studies have attempted to examine this domain of functioning in people with psychosis, particularly in India. A total of 71 patients with psychosis, (both early and established psychosis), and 140 age, gender and education-matched healthy controls were assessed using the Positive and Negative Symptom Scale, Hospital Anxiety and Depression scale, and Addenbrooke's Cognitive Examination. PM was assessed using the Cambridge Prospective Memory Test and the Prospective and Retrospective Memory Questionnaire (PRMQ). Group differences were evaluated using Mann-Whitney U-tests. Significantly greater cognitive deficits, higher anxiety and depression were evident in the psychosis group compared with controls. The psychosis group performed significantly poorer on both time- and event-based tests in CAMPROMPT than controls. These differences remained when controlling for age, education, general cognitive functioning and mood. The subjective measure of PM (PRMQ) did not differentiate the two groups. The PM performance of early and established psychosis patients was similar. Comparisons with cross-cultural data (PRMQ UK norms and CAMPROMPT and PRMQ Chinese data) revealed important differences in PM performance. Individuals with psychosis have significant deficits in both time- and event-based PM. CAMPROMPT emerged as a more sensitive PM measure compared with PRMQ. Results from cross-cultural comparisons underscore the need for cultural contextualization of assessments.

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.

Topography, power, and current source density of θ oscillations during reward processing as markers for alcohol dependence.

Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. Event-related theta band (3.0-7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200-500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control.

Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.

Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10⁻6). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10⁻4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.

Reduced resource optimization in male alcoholics: N400 in a lexical decision paradigm.

BACKGROUND: Event Related Potential (ERP) studies have highlighted some measures, notably P3 amplitude, that are associated with both state and trait deficits in alcoholism, while studies examining N400 amplitude in alcoholism are few. The present study aims to examine differences in the N400 component, an electrophysiological correlate of semantic priming, in event-related potentials from a lexical decision task in 87 alcohol dependent subjects and 57 community controls. METHODS: Each subject was presented with 300 stimuli sequentially in a quasi-randomized design, where 150 stimuli were words and 150 were non-words. The subjects made a lexical decision indicating the word/non-word status with a button press. Among the words, 50 words (primed) were always preceded by their antonyms (prime, n=50), whereas the remaining 50 words were unrelated. N400 amplitude and latency measures were compiled from ERPs to the primed and unprimed words. Corresponding reaction time (RT) and response characteristics were also analyzed. RESULTS: Control subjects revealed a significant attenuation of the N400 response to the primed word when compared to the unprimed word. Significantly less attenuation was observed in alcohol dependent subjects. No significant group differences were seen for latency and behavioral measures. All subjects had slower RT for unprimed words compared to primed words; however significantly less RT savings between the unprimed and primed condition was noted for alcoholics. CONCLUSIONS: These results suggest a reduced flexibility in the cognitive networks and a lack of resource optimization in alcoholics. The reduced attenuation of N400 during the primed condition in the alcohol dependent subjects may reflect an inability to engage similar neuronal substrates associated with semantic relatedness as seen in the controls. As diminished N400 attenuation during priming is observed in both alcoholics and high risk subjects, it may be a marker of risk and a good endophenotype for alcoholism.

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.

BACKGROUND: Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. METHODS: We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. RESULTS: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. CONCLUSIONS: Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

Priming deficiency in male subjects at risk for alcoholism: the N4 during a lexical decision task.

BACKGROUND: While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics. METHOD: A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered. RESULTS: A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli. CONCLUSION: The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.

EEG coherence: topography and frequency structure.

Topographical patterns of bipolar EEG coherence are frequency specific, indicating the presence of diverse neuroanatomical and neurophysiological factors in EEG production. Bipolar EEG coherence values were calculated at 50 frequency bins ranging from 3 to 28 Hz for 39 coherence pairs. Data were derived from 4.25 min of resting EEG obtained from 106 healthy adult male subjects and analyzed in 0.5 Hz bins by Fourier transform methods. Frequency bands were clearly separated at 8.5 and 13 Hz, with a less distinct separations at 6 and 20 Hz. Within pair (non-topographic) and across pair (topographic), measures gave similar patterns of separation. Significant pathways were primarily anterior-posterior interhemispheric or perpendicular to the anterior-posterior axis. There was little difference between left and right for comparable pairs. Theta band coherent activity involves distinct midline and temporal sources, with temporal sources showing anterior/posterior differentiation. In contrast, alpha activity has a distinct posterior focus, while beta activity shows no clear global structure. A spatially homogeneous model based on characteristics of thalamocortical connectivity accounts for much of the data, but departures from the model indicate the contribution of other neural factors to coherence.

EEG power spectra differentiate positive and negative subgroups in neuroleptic-naive schizophrenia patients.

Electroencephalogram spectral power was estimated at 30 scalp locations in 28 neuroleptic-naive, recent-onset schizophrenia (NRS) patients and 25 healthy comparison subjects in the resting eyes closed condition. Weighted relative power values in the various bandwidths were initially compared between NRS subjects and comparison subjects and subsequently between the positive symptom subgroup, negative symptom subgroup, and comparison subjects, to look for characteristic spectral power profiles of the homogeneous symptom subgroups. Significant differences were noted especially in alpha2, delta, and theta bands between NRS patients and healthy comparison subjects, while the positive symptom and negative symptom subgroups showed characteristic spectral power profiles in alpha1, alpha2, delta, and theta bands.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

An Exploration of Attitudes Toward Dogs among College Students in Bangalore, India.

Conversations in the field of anthrozoology include treatment and distinction of food animals, animals as workers versus pests, and most recently, emerging pet trends including the practice of pet parenting. This paper explores attitudes toward pet dogs in the shared social space of urban India. The data include 375 pen-and-paper surveys from students at CHRIST (Deemed to be University) in Bangalore, India. Reflecting upon Serpell's biaxial concept of dogs as a relationship of affect and utility, the paper considers the growing trend of pet dog keeping in urban spaces and the increased use of affiliative words to describe these relationships. The paper also explores potential sex differences in attitudes towards pet and stray dogs. Ultimately, these findings suggest that the presence of and affiliation with pet dogs, with reduced utility and increased affect, is symptomatic of cultural changes typical of societies encountering the second demographic transition. Despite this, sex differences as expected based upon evolutionary principles, remain present, with women more likely to emphasize health and welfare and men more likely to emphasize bravery and risk taking.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Theta oscillations during the processing of monetary loss and gain: a perspective on gender and impulsivity.

Event-related oscillations (EROs) have proved to be very useful in the understanding of a variety of neurocognitive processes including reward/outcome processing. In the present study, theta power (4.0-7.0 Hz) following outcome stimuli in the time window of the N2-P3 complex (200-500 ms) was analyzed in healthy normals (20 males and 20 females) while performing a gambling task that involved monetary loss and gain. The main aim was to analyze outcome processing in terms of event-related theta power in the context of valence, amount, gender, and impulsivity. The S-transform was used for the signal processing of the ERO data in terms of time-frequency-power. Results from filtered waveforms showed a partially consistent phase-alignment of the increased theta activity corresponding to N2 and P3 components following the outcome stimuli. Gain conditions produced more theta power than loss conditions. While there was anterior involvement in both gain and loss, posterior activation was stronger during gain conditions than during loss conditions. Females exhibited posterior maxima during gain conditions while males had an anterior maxima during both loss and gain conditions. The current source density of theta activity in females involved larger areas with a bilateral frontal activity while males predominantly had a frontal midline activity. Theta power was significantly higher in females than males across all conditions. Low theta (4.0-5.5 Hz) predominantly contributed to the posterior activity during gain conditions. High theta (5.5-7.0 Hz) was more associated with impulsivity measures than low theta activity. These findings may offer valuable clues to understand outcome processing, impulsivity, and gender differences.

Heritability of EEG coherence in a large sib-pair population.

The additive genetic heritability of bipolar EEG coherence in a sample of 305 non-twin sibships comprising 690 individuals (age range 7-65) was estimated. Heritabilities were examined in 6 frequency bands for each of 15 coherence pairs, both interhemispheric and intrahemispheric. The heritabilities of the bipolar EEG coherence ranged from 0.22 to 0.63 in 79 of the 90 phenotypes which had coherences high enough to provide meaningful values for the estimation of heritability. Heritabilities were greatest in the low and high alpha frequency bands, while theta and beta bands had comparable heritabilities. Coherences themselves were greatest in the low and high alpha frequency bands, while theta coherences were somewhat larger than beta. Higher heritability values were not associated with higher coherences. The examination of bivariate genetic correlations suggests that there is a difference between theta and alpha bands in genetic control of interhemispheric coherence.

Genetic influences on bipolar EEG power spectra.

The EEG bipolar power spectra provide more localization than spectral measures obtained from monopolar referencing strategies, and have been shown to be useful endophenotypes of psychiatric disorders such as alcoholism. We estimated the additive genetic heritability of resting bipolar EEG power spectra in a large sample of non-twin sibling pairs. The corresponding heritabilities ranged between 0.220 and 0.647 and were highly significant at all 38 electrode pairs for theta (3-7 Hz), low-alpha (7-9 Hz), high-alpha (9-12 Hz), low-beta (12-16 Hz), middle-beta (16-20 Hz) and high-beta (20-28 Hz) frequency bands. The heritabilities were the highest in the high-alpha and low-beta bands at most electrode pairs. The heritabilities were most variable across the head in the three beta bands. Other heritability patterns were also identified within each frequency band. Our results suggest that substantial proportions of the variability in the bipolar EEG measures are explained by genetic factors.