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Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.
Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).
The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.
Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
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.
Disorders of behavior represent some of the most common and disabling diseases affecting humankind; however, despite their worldwide distribution, genetic influences on these illnesses are often overlooked by families and mental health professionals. Psychiatric genetics is a rapidly advancing field, elucidating the varied roles of specific genes and their interactions in brain development and dysregulation. Principles of Psychiatric Genetics includes 22 disorder-based chapters covering, amongst other conditions, schizophrenia, mood disorders, anxiety disorders, Alzheimer's disease, learning and developmental disorders, eating disorders and personality disorders. Supporting chapters focus on issues of genetic epidemiology, molecular and statistical methods, pharmacogenetics, epigenetics, gene expression studies, online genetic databases and ethical issues. Written by an international team of contributors, and fully updated with the latest results from genome-wide association studies, this comprehensive text is an indispensable reference for psychiatrists, neurologists, psychologists and anyone involved in psychiatric genetic studies.
Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain.
CSF and plasma GABA was measured in patients with bipolar affective illness and matched controls. There was no correlation between CSF and plasma GABA in 10 pairs of simultaneously obtained samples. Plasma GABA was significantly lower in a group of 10 euthymic medication-free bipolar patients compared to 41 normal volunteers (P <.02). This finding was replicated in a second study involving 6 patients and 10 normal volunteers. Twin studies showed a high correlation between members of 11 monozygotic twin pairs (P <.008). Diurnal variation was minimal, but bimonthly sampling over one year revealed somewhat higher values in the late summer compared to late winter.
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