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PubMed2002

The importance of cultural inheritance in psychiatric genetics.

Cultural inheritance, a genetic-based inheritance system transmitted by the brain, has previously been proposed to underlie normal behaviour and mental disorders. In cultural inheritance epigenetic mechanisms are involved in gene expression. This paper proposes that since there are marked epigenetic mechanisms involved in the expression of genes underlying primary (idiopathic) mental disorders, epimutations, rather than genetic mutations, underlie these disorders.

Animals↗
PubMed1998

Anna-Monika-Prize paper. Major depression and the environment: a psychiatric genetic perspective.

Genetic factors can interact with environmental factors to influence the vulnerability to major depression (MD) in subtle ways. I explore two such mechanisms: "genetic control of sensitivity to the environment," and "genetic control of exposure to the environment." "Genetic control of sensitivity to the environment" suggests that genes, in part, render individuals relatively vulnerable or relatively invulnerable to the pathogenic effects of environmental stress. In support of this hypothesis, evidence is presented that the depressogenic effect of stressful life events is substantially greater in those at high versus low genetic risk to the MD. "Genetic control of exposure to the environment" suggests that genetic factors influence the probability that individuals will select themselves into high vs. low risk environments. In support of this hypothesis, evidence from a population based twin study suggests that certain classes of stressful life events are modestly heritable. The genetic risk factors for MD in part express themselves by influencing the probability that individuals will experience stressful life events, particularly of an interpersonal nature.

Depressive Disorder↗
PubMed2003

The future of psychiatric genetics.

Geneticists have been predicting that advances in their discipline will revolutionize the understanding of human disease and behavior. While there has been considerable progress in disorders showing simple, Mendelian patterns of inheritance, expectations have yet to be fulfilled for disorders and traits showing complex inheritance. In this article, we consider the difficulties that complex diseases pose to genetic research, discuss progress and make suggestions regarding future directions.

Animals↗
PubMed2005

Psychiatric genetics--the new era: genetic research and some clinical implications.

Impressive advances in the last decade have been made in the genetics and neuroscience of neuropsychiatric illness. Synergies between complex genetics, elaboration of intermediate phenotypes (Egan et al. (2004) Schizophrenia. London: Blackwell) and novel applications in neuroimaging (Bookheimer et al. (2000) N Engl J Med, 343, 450-456) are revealing the effects of positively associated disease alleles on aspects of neurological function. Genes such as NRG-1, DISC1, RGS4, COMT, PRODH, DTNBP1, G72, DAAO, GRM3 (Harrison and Weinberger (2005) Mol Psychiatry, 10, 40-68) and others have been implicated in schizophrenia along with 5-HTTPR (Ogilvie et al. (1996) Lancet, 347, 731-733; Caspi et al. (2003) Science, 301, 386-389) and BDNF (Geller et al. (2004) Am J Psychiatry, 161, 1698-1700) in affective disorders. As the genetics and complex neurocircuits of these and disorders are being untangled, parallel applications in pharmacogenomics and gene-based drug metabolism are shaping a drive for personalized medicine. Genetic research and pharmacogenomics suggest that the subcategorization of individuals based on various sets of susceptibility alleles will make the treatment of neuropsychiatric and other illnesses more predictable and effective.

Chromosomes, Human↗
PubMed1986

Clinical methods in psychiatric genetics. III. Environmental stratification may simulate a genetic effect in adoption studies.

In adoption studies, the possibility of inadvertent matching between biological and adoptive parents for some environmental variable (known or unknown) correlated with illness must be considered. We examine such bias quantitatively and show how a genetic effect can be simulated. Existence of a genetic effect which is independent of environmental correlation can be accepted, when the frequency of a disease in adoptees who have a biological parent affected and no adoptive parents affected is significantly greater than the frequency of the disease in adoptees who have an adopted parent affected and no biological parents affected. The published data on schizophrenia, alcoholism, and criminality do not exclude the possibility of undetected environmental correlations simulating a genetic effect, according to this direct criterion.

Adoption↗
PubMed1986

Clinical methods in psychiatric genetics. I. Robustness of genetic marker investigative strategies.

Population stratification, secondary effects of illness or treatment, biological heterogeneity of a clinical syndrome, or complex biology underlying a syndrome (where only one component is measured) are conditions which may obscure the association of a genetic risk factor with a clinical syndrome. We consider several investigative strategies under each of these conditions. Only segregation-based paradigms are robust to genetic heterogeneity and population stratification. But secondary effects on the risk factor produced by illness or treatment require other strategies for their detection.

Chromosome Aberrations↗