The first significant twin study of affective disorders and neurosis was conducted by Bertelsen (1979). In addition, MZ twins share the same placental circulation. One problem for the twin method is that exposure to the same family environment may have differential effects on MZ twins as compared with DZ twins. Twin studies can give information about the effects of shared (family) environment as well as non-shared (unique, specific) environment.
Prenatal and postnatal familial environmental factors are assumed to be a constant in both sets of twins. The central assumption of these studies is that monozygotic twins share the same genes, whilst dizygotic twins have on average 50% of their genes in common. Twin studies compare concordance rates for illness in pairs of monozygotic (MZ) and dizygotic twins (DZ). Larry Rifkin, Hugh Gurling, in Biological Aspects of Affective Disorders, 1991 9.3.2 Twin studies However, in the majority of cases, it is likely that variability is multigenetic in origin and thus poses challenges in developing predictive tests. Twin studies with other drugs, including antipyrine, phenytoin, halothane, and phenylbutazone have all shown that genetic factors are the main determinants of interindividual variation in metabolism. We now know that individuals who are “slow acetylators” are at greater risk of toxicity with compounds such as sulphonamides and aromatic amine carcinogens, and with isoniazid, which leads to hepatic toxicity and peripheral neuropathy. This was later confirmed to be due, at least in part, to two distinct acetylation phenotypes (slow and rapid) that are determined by polymorphisms in the N-acetyltransferase gene. In a study comparing metabolism between five pairs of MZ and DZ twins, investigators showed that the metabolism of isoniazid was far less variable in the former than in the latter. One of the first twin studies to identify a pharmacogenetic phenotype for ADR involved the antituberculosis (TB) drug isoniazid. It can be assumed that twins are raised in identical environments therefore, any greater similarity of a trait shared between MZ twins compared to DZ twins can be attributed to genetics. Twin studies compare the similarity of a trait between monozygotic (MZ) twins who share 100% genetic identity and that of dizygotic (DZ) twins who on average share only 50% of the genome. Twin studies are a valuable tool to assess the relative contribution of genetic and environmental factors to variation in complex phenotypes, including drug response. Munir Pirmohamed, in Handbook of Pharmacogenomics and Stratified Medicine, 2014 20.1.3.1 Twin Studies Based on these findings, the most promising marker for BD in adult HR appears to be verbal memory. The greater genetic variation between dizygotic twin pairs may explain why this sample of co-twins showed less impairment relative to the healthy comparison group than the monozygotic twins in the earlier study. Unlike the previous twin study, this study included nonidentical twin pairs. However, after adjusting for gender, the authors did find a significant deficit in verbal learning in the unaffected female co-twins, and once again impairment was shown in delayed verbal recall. Another larger twin study found no significant deficits between unaffected co-twins and healthy twin pairs in tests of attention, working memory, verbal or nonverbal memory, or verbal learning ( Kieseppä et al., 2005).
Both discordant twins performed significantly worse than control twins, but only the affected twin presented short-delay verbal memory deficits.
The assessment of cognitive functions in seven adult monozygotic twin pairs discordant for BD showed that the unaffected twins with an affected sibling performed significantly worse than control twins on measures of working memory and attention/mental control ( Gourovitch et al., 1999 ). To date, there are no published twin studies in pediatric offspring of parents with BD, or even on pediatric BD. Twin studies have the advantage of taking into account both genetic and environmental factors, and may be more likely to outline the genetic basis of cognitive deficits in HR. Soares, in Bipolar Disorder Vulnerability, 2018 Twin studies
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