Genetic patterns of correlation among subcortical volumes in humans: results from a magnetic resonance imaging twin study.

Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes.

Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8.

Background: Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g.

Positive symptoms of psychosis correlate with expression of ubiquitin proteasome genes in peripheral blood.

Several brain- and blood-based gene expression studies in patients with psychotic disorders (e.g., schizophrenia) have identified genes in the ubiquitin proteasome system (UPS) pathway as putative biomarkers.

Heritability of brain ventricle volume: converging evidence from inconsistent results.

Twin studies generally show great consistency for the heritability of brain structures. Ironically, the lateral ventricles--perhaps the most reliably measured brain regions of interest--are the most inconsistent when it comes to estimating genetic influences on their volume. Heritability estimates in twin studies have ranged from zero to almost 0.

Does parental education have a moderating effect on the genetic and environmental influences of general cognitive ability in early adulthood?

Hereditary influences account for a substantial proportion of the variance in many cognitive abilities. However, there is increasing recognition that the relative importance of genetic and environmental influences may vary across different socioeconomic levels. The overall goal of the present study was to examine whether parental education has a moderating effect on genetic and environmental influences of general cognitive ability in early adulthood (age 19.

Genetic and environmental influences on cortisol regulation across days and contexts in middle-aged men.

Cortisol is an indicator of hypothalamic-pituitary-adrenal axis responsivity to stress, but few twin studies have examined the heritability of cortisol concentrations in adults across the diurnal cycle and in different contexts. Saliva samples were provided by 783 middle-aged male twins on one laboratory and two home days as part of the Vietnam Era Twin Study of Aging. Significant cortisol heritability estimates were found for laboratory measures only: awakening (.

Associations between jet lag and cortisol diurnal rhythms after domestic travel.

Objective: Millions of adults in the United States travel abruptly across time zones each year. Nevertheless, the impact of traveling over relatively short distances (across 3 or fewer time zones) on diurnal patterning of typical physiological response patterns has yet to be studied in a large, epidemiological sample.

Design: The current research focuses on 764 middle-aged men comparing variations in diurnal cortisol regulation based on number of time zones traveled eastward or westward the day before.

Genetic vulnerability and phenotypic expression of depression and risk for ischemic heart disease in the Vietnam era twin study of aging.

Objective: To determine if depression contributes to incident heart disease after accounting for genetic, behavioral, and medical factors associated with both conditions.

Methods: We used a prospective twin study with a 12-year follow-up. In 1992, lifetime diagnosis of depression was assessed in 1159 male-male twins and merged with longitudinal health data from the Vietnam Era Twin Registry Study of Aging.

Salivary cortisol and prefrontal cortical thickness in middle-aged men: A twin study.

Although glucocorticoid receptors are highly expressed in the prefrontal cortex, the hippocampus remains the predominant focus in the literature examining relationships between cortisol and brain. We examined phenotypic and genetic associations of cortisol levels with the thickness of prefrontal and anterior cingulate cortex regions, and with hippocampal volume in a sample of 388 middle-aged male twins who were 51-59 years old. Small but significant negative phenotypic associations were found between cortisol levels and the thickness of left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal regions, and right dorsolateral (superior frontal gyrus) and medial orbital frontal cortex.

Introduction to the special issue, pathways between genes, brain, and behavior.

In the past 10 years or so, with the sequencing of the human genome and rapid advances in the development of high throughput techniques, the field of behavior genetics has increasingly moved toward the detection of actual genes and environmental factors. However, the field is still in the relatively early stages of understanding some of the basic facts about the complex genetic underpinnings of brain structure and function and their relationship to behavior. The 15 articles in this special issue were selected to represent the diversity of methodologies applied to the complexity of pathways linking genes, brain, and behavior.

Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study.

Background: We examined cognitive deficits before and after onset of schizophrenia in a longitudinal study that: 1) covers a long time interval; 2) minimizes test unreliability by including the identical measure at both childhood and post-onset cognitive assessments; and 3) minimizes bias by utilizing a population-based sample in which participants were selected neither for signs of illness in childhood nor for being at risk for schizophrenia.

Methods: Participants in the present study, Developmental Insult and Brain Anomaly in Schizophrenia (DIBS), were ascertained from an earlier epidemiologic study conducted in Oakland, CA. The original version of the Peabody Picture Vocabulary Test (PPVT), a test of receptive vocabulary, was administered at age 5 or 9 and repeated as part of the DIBS study at an average age of 40.

Cortical thickness is influenced by regionally specific genetic factors.

Background: Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the patterning of those genetic influences, i.e.

Genetic and environmental influences on the size of specific brain regions in midlife: the VETSA MRI study.

The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs).

Alternatively Spliced Genes as Biomarkers for Schizophrenia, Bipolar Disorder and Psychosis: A Blood-Based Spliceome-Profiling Exploratory Study.

OBJECTIVE: Transcriptomic biomarkers of psychiatric diseases obtained from a query of peripheral tissues that are clinically accessible (e.g., blood cells instead of post-mortem brain tissue) have substantial practical appeal to discern the molecular subtypes of common complex diseases such as major psychosis.

Genes determine stability and the environment determines change in cognitive ability during 35 years of adulthood.

Previous research has demonstrated stability of cognitive ability and marked heritability during adulthood, but questions remain about the extent to which genetic factors account for this stability. We conducted a 35-year longitudinal assessment of general cognitive ability using the Armed Forces Qualification Test administered to 7,232 male twins in early adulthood and readministered to a subset of 1,237 twins during late middle age. The proportion of variance in cognitive functioning explained by genetic factors was .

Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: convergent pathway analysis findings from two independent samples.

Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control = 8) and Taiwan (SCZ = 11, BPD = 14, control = 16).

Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia.

Objective: Executive dysfunction is one of the most prominent and functionally important cognitive deficits in schizophrenia. Although strong associations have been identified between executive impairments and structural and functional prefrontal cortical deficits, the etiological factors that contribute to disruption of this important cognitive domain remain unclear. Increasing evidence suggests that schizophrenia has a neurodevelopmental etiology, and several prenatal infections have been associated with risk of this disorder.

Distinct genetic influences on cortical surface area and cortical thickness.

Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness.

Prenatal infection and cavum septum pellucidum in adult schizophrenia.

Increased length of the cavum septum pellucidum (CSP) and in utero infection are each associated with increased risk of schizophrenia. Hence, we examined whether prenatal infections are related to CSP length in schizophrenia patients. In a well-characterized birth cohort, in utero infection was assessed using serologic biomarkers or physician diagnoses.

Factor structure of planning and problem-solving: a behavioral genetic analysis of the Tower of London task in middle-aged twins.

We examined the genetic architecture of a Tower of London test of planning and problem-solving in 690 middle-aged male twins. Phenotypic analyses revealed only one general factor, but the best-fitting genetic model indicated two correlated genetic factors: speed and efficiency. One variable-number of attempts required to mentally figure the puzzles-loaded on both factors.

Ordered subsets linkage analysis of antisocial behavior in substance use disorder among participants in the Collaborative Study on the Genetics of Alcoholism.

Heterogeneity in complex diseases such as Substance Use Disorder (SUD) reduces the power to detect linkage and makes replication of findings in other populations unlikely. It is therefore critical to refine the phenotype and use methods that account for genetic heterogeneity between families. SUD was operationalized as diagnosis of abuse or dependence to alcohol and/or any one of five illicit substances.

Storage and executive components of working memory: integrating cognitive psychology and behavior genetics in the study of aging.

We combined experimental cognitive and behavior genetic methods to investigate storage and executive components of working memory in 663 middle-aged male twins. A single latent factor model indicated that digits forward (storage) and two-digit transformation (executive + storage) scores were influenced by the same genes. Additional executive demands in digit transformation appeared to increase the variance of individual genetic differences from 25% for digits forward to 48% and 53% for the digit transformation scores.

IQ decline in cross-sectional studies of schizophrenia: methodology and interpretation.

Some researchers have compared neuropsychological performance in schizophrenia groups with and without presumed IQ decline. Inherent in this approach is an assumption that group differences are due to different IQ trajectories (stable vs. declining), but neuropsychological differences could be a function of current IQ regardless of the presence or absence of previous IQ decline.

Apolipoprotein E genotype and memory in the sixth decade of life.

Background: Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, epsilon 4 carriers may manifest greater cognitive asymmetries than non-epsilon 4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound.