So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

This chapter suggests that delinquency conceals two distinct categories of individuals, each with a unique natural history and etiology: A small group engages in antisocial behavior of one sort or another at every life stage, whereas a larger group is antisocial only during adolescence. According to the theory of life-course-persistent antisocial behavior, children's neuropsychological problems interact cumulatively with their criminogenic environments across development, culminating m a pathological personality. According to the theory of adolescence-limited antisocial behavior, a contemporary maturity gap encourages teens to mimic antisocial behavior in ways that are normative and adjustive. There are marked individual differences in the stability of antisocial behavior. The chapter reviews the mysterious relationship between age and antisocial behavior. Some youths who refrain from antisocial behavior may, for some reason, not sense the maturity gap and therefore lack the hypothesized motivation for experimenting with crime.

/pdf/adolescence-limited-and-life-course-persistent-antisocial-52vil00qlw.pdf

Adolescence-limited and life-course-persistent antisocial behavior: A developmental taxonomy.

In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

/pdf/influence-of-life-stress-on-depression-moderation-by-a-43dxsjf74s.pdf

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene

The Autism Diagnostic Observation Schedule-Generic (ADOS-G) is a semistructured, standardized assessment of social interaction, communication, play, and imaginative use of materials for individuals suspected of having autism spectrum disorders. The observational schedule consists of four 30-minute modules, each designed to be administered to different individuals according to their level of expressive language. Psychometric data are presented for 223 children and adults with Autistic Disorder (autism), Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) or nonspectrum diagnoses. Within each module, diagnostic groups were equivalent on expressive language level. Results indicate substantial interrater and test-retest reliability for individual items, excellent interrater reliability within domains and excellent internal consistency. Comparisons of means indicated consistent differentiation of autism and PDDNOS from nonspectrum individuals, with some, but less consistent, differentiation of autism from PDDNOS. A priori operationalization of DSM-IV/ICD-10 criteria, factor analyses, and ROC curves were used to generate diagnostic algorithms with thresholds set for autism and broader autism spectrum/PDD. Algorithm sensitivities and specificities for autism and PDDNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS.

/pdf/the-autism-diagnostic-observation-schedule-generic-a-o50oqma4kk.pdf

The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism.

The emerging field of emotion regulation studies how individuals influence which emotions they have, when they have them, and how they experience and express them. This review takes an evolutionary perspective and characterizes emotion in terms of response tendencies. Emotion regulation is denned and distinguished from coping, mood regulation, defense, and affect regulation. In the increasingly specialized discipline of psychology, the field of emotion regulation cuts across traditional boundaries and provides common ground. According to a process model of emotion regulation, emotion may be regulated at five points in the emotion generative process: (a) selection of the situation, (b) modification of the situation, (c) deployment of attention, (d) change of cognitions, and (e) modulation of responses. The field of emotion regulation promises new insights into age-old questions about how people manage their emotions.

http://www.elaborer.org/cours/A13/lectures/Gross1998.pdf

The emerging field of emotion regulation: An integrative review.

Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.

/pdf/the-endophenotype-concept-in-psychiatry-etymology-and-2w2rrj3jlx.pdf

The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033291700028099

Autism as a strongly genetic disorder: evidence from a British twin study.

Scores on the Wechsler Intelligence Scale for Children were analyzed in a sample of 7-year-old twins from the National Col- laborative Perinatal Project. A substantial proportion of the twins were raised in families living near or below the poverty level. Biometric analyses were conducted using models allowing for components attrib- utable to the additive effects of genotype, shared environment, and non- shared environment to interact with socioeconomic status (SES) measured as a continuous variable. Results demonstrate that the proportions of IQ variance attributable to genes and environment vary nonlinearly with SES. The models suggest that in impoverished families, 60% of the vari- ance in IQ is accounted for by the shared environment, and the contri- bution of genes is close to zero; in affluent families, the result is almost exactly the reverse.

Socioeconomic Status Modifies Heritability of IQ in Young Children

Twin studies have been vital for establishing an important genetic contribution to the etiology of schizophrenia. The five newest studies since 1995 from Europe and Japan have confirmed earlier findings. They yielded probandwise concordance rates of 41-65% in monozygotic (MZ) pairs and 0-28% in dizygotic (DZ) pairs, and heritability estimates of approximately 80-85%. Twin studies are also valuable for investigating the etiological relationships between schizophrenia and other disorders, and the genetic basis of clinical heterogeneity within schizophrenia. Studies of discordant MZ pairs provide further insights into non-inherited factors that contribute to the multifactorial etiology of this disorder. More recently, twin studies have begun to be used to directly investigate molecular genetic and epigenetic processes underlying schizophrenia.

Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics.

'The book will appeal to a variety of readers. The history of the illness, its diagnoses, epidemiology, demography, inheritance and environmental stresses would be of general interest. The anguished voices describing personal accounts of the symptoms would probably appeal more to non-professional readers, perhaps patients and their families...To a Psychiatrist, his description of genetic and environmental research is comprehensive...' - Journal of Neurology, Neurosurgery and Psychiatry 'His book is comprehensive, compassionate and easy to read.' - New Scientist

Irving I. Gottesman

Papers

The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

Autism as a strongly genetic disorder: evidence from a British twin study.

Socioeconomic Status Modifies Heritability of IQ in Young Children

Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics.

Schizophrenia Genesis: The Origins of Madness