Does intra-uterine growth discordance predict differential risk for adult psychiatric disorder in a population-based sample of monozygotic twins?

The study of discordant monozygotic twins may identify important developmental risk factors for adult psychiatric disorder. Differential experience in utero is one candidate environmental risk factor that may distinguish monozygotic twins. In this report, we examine whether intra-pair differences in birth weight predicts discordance for adult psychiatric disorders in 527 female monozygotic twin pairs from a population-based twin registry. Twins were personally interviewed about their lifetime history of DSM-III-R alcoholism, anorexia nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic disorder, social phobia and simple phobia. Birth weight was estimated from birth certificates, or from retrospective maternal, paternal and self-reports. Conditional logistic regression is used to characterize the association between intra-pair differences in birth weight and discordance for psychiatric disorder in monozygotic twins. The twin with the heavier birth weight in discordant pairs is (insignificantly) more likely to have a history of alcoholism or bulimia. The twin with the lighter birth weight in discordant pairs is (insignificantly) more likely to have a history of major depression, simple phobia, panic disorder, anorexia nervosa, social phobia or generalized anxiety disorder. For all psychiatric disorders examined, the lighter (or heavier) co-twin at birth is not systematically the affected twin within discordant pairs.     

DOUBLE BIND: A STUDY OF TWO PAIRS OF FEMALE MONOZYGOTIC TWINS CONCORDANT FOR ANOREXIA NERVOSA

ABSTRACT The cases of two pairs of female monozygotic twins concordant for anorexia nervosa are considered in order to explore the interrelationship between the psychodynamics of the twin relationship and the psychopathology of anorexia. It is suggested that twins face a dual task of separation-individuation - from mother and from the other twin - and that separation- individuation between monozygotic twins presents particular difficulties. Anorexia nervosa may represent an attempt to avoid separation by means of a retreat to a pre-adolescent state in which differences, envy and rivalry can be denied.     

Individual-specific risk factors for anorexia nervosa: a pilot study using a discordant sister-pair design

BACKGROUND: The aim of this pilot study was to examine which unique factors (genetic and environmental) increase the risk for developing anorexia nervosa by using a case-control design of discordant sister pairs. METHODS: Forty-five sister-pairs, one of whom had anorexia nervosa and the other did not, were recruited. Both sisters completed the Oxford Risk Factor Interview for Eating Disorders and measures for eating disorder traits, and sib-pair differences. Blood or cheek cell samples were taken for genetic analysis. Statistical power of the genetic analysis of discordant same-sex siblings was calculated using a specially written program, DISCORD. RESULTS: The sisters with anorexia nervosa differed from their healthy sisters in terms of personal vulnerability traits and exposure to high parental expectations and sexual abuse. Factors within the dieting risk domain did not differ. However, there was evidence of poor feeding in childhood. No difference in the distribution of genotypes or alleles of the DRD4, COMT, the 5HT2A and 5HT2C receptor genes was detected. These results are preliminary because our calculations indicate that there is insufficient power to detect the expected effect on risk with this sample size. CONCLUSIONS: A combination of intrinsic and extrinsic factors increases the risk of developing anorexia nervosa. It would, therefore, be informative to undertake a larger study to examine in more detail the unique genetic and environmental factors that are associated with various forms of eating disorders.     

Analysis of the -1438 G/A polymorphism of the 5-HT2A serotonin receptor gene in bulimia nervosa patients with or without a history of anorexia nervosa

A single nucleotide polymorphism (-1438 G/A) located 1438 base pairs upstream of the consensus start site of the 5-HT2A receptor gene has been reported. The hypothesis that this gene polymorphism may be a susceptibility factor in bulimia nervosa was explored in a female population of purgative bulimics. Bulimia nervosa patients who have suffered preceding anorexia nervosa episodes formed the so-called previous anorexia nervosa bulimic patient group. At variance with some previous reports, when the frequency distribution of genotypes and alleles was compared in patients and controls, no differences were detected regardless of whether the bulimia nervosa patients had suffered prior anorexia nervosa episodes.     

Are thyrogastric autoantibodies associated with an increased susceptibility to developing type 1 (insulin-dependent) diabetes? A study in identical twins

To examine whether the presence of thyrogastric autoantibodies is associated with an increased susceptibility towards developing type 1 diabetes we have tested for thyroid (microsomal and thyroglobulin) and gastric-parietal cell antibodies in 86 pairs of identical twins, 47 discordant and 39 concordant for type 1 diabetes. Autoantibodies were detected in both twins of a pair in 35 and in neither twin in 45 pairs. In only 6 pairs (3 discordant) was there a discrepancy in the antibody results between co-twins. The frequency of antibodies was similar in twin pairs discordant, (21/44, 48%), and concordant, (14/36, 39%), for diabetes. Thyrogastric antibodies were not more frequent in pairs that were female, diagnosed above the age of 20, or had HLA DR3 as opposed to DR4. We conclude that thyrogastric autoantibodies are common in both type 1 diabetic patients and their non-diabetic identical twins. Their presence appears to be genetically determined but does not increase the susceptibility of developing diabetes. The presence of autoantibodies does not appear to indicate a separate aetiological type of diabetes.     

Anorexia nervosa in monozygotic twins

Which is more important, hereditary factors or psychological environment factors, in the etiology of anorexia nervosa? The question is studied by considering 7 cases of anorexia nervosa in monozygotic twins of the authors' own practice. In 5 of 7 cases, only 1 of a set of twins was found to be suffering from anorexia nervosa. On the other hand, in 2 of 7 cases, both twins were diagnosed as having anorexia nervosa. Even in the concordant cases studied by the authors, however, the quality or degree of anorexia nervosa in each case was different. Therefore, even given the existence of concordant cases, without inquiring precisely into the quality or degree of anorexia nervosa, it is not possible to conclude that hereditary factors play a determining role in the etiology of anorexia nervosa.     

Environmental Factors in Obsessive-Compulsive Behavior: Evidence from Discordant and Concordant Monozygotic Twins

To investigate environmental factors that protect against or exacerbate obsessive-compulsive (OC) symptoms, we selected 25 monozygotic (MZ) twin pairs discordant, 17 MZ twin pairs concordant high and 34 MZ pairs concordant low on OC symptoms from a large longitudinal Dutch sample of adult twin pairs and their family members, applying stringent criteria for OC symptomatology. Data were collected on psychopathology, family structure, health, lifestyle, birth complications and life events. Unique environmental factors were studied using within-discordant MZ pair comparisons, whereas between-concordant MZ pair comparisons were used to study environmental factors that are shared by the twins of an MZ pair. The high-scoring MZ twins of the discordant group reported more life events (especially sexual abuse) than their low-scoring twin-siblings. The between-pair comparisons showed lower birth weight in the discordant MZ pairs than in the concordant MZ pairs. Further, the concordant high MZ pairs as well as their spouses had a lower educational level than the two other groups. On scale scores of anxious-depression, neuroticism, and somatic complaints, concordant high MZ pairs showed highest scores, and the discordant MZ pairs scored intermediate, except for neuroticism, on which the high-scoring twins of discordant MZ pairs were equal to the concordant high pairs. Discordance on psychological scale scores between the concordant MZ pairs was evident from 1991 onward, and within the discordant MZ pairs from 1997 onward, confirming previous reports of an association of early-onset OC symptoms with higher genetic load. Parent scores of OC symptoms and anxious-depression suggested intermediate genetic load in the discordant MZ group. In conclusion, this study reports on both unique and shared environmental factors associated with OC symptomatology. Whether these factors operate in addition to or in interaction with genetic disposition is to be elucidated in future studies. Edited by Tatiana Foroud.     

Healthy monozygous twins do not recognize identical T cell epitopes on the myelin basic protein autoantigen

The T cell response against myelin basic protein (MBP) has been extensively studied in humans because of its putative role in the pathophysiology of multiple sclerosis (MS). Higher concordance rates in monozygous twins as well as an increased risk in relatives suggest the role of genetic factors in MS susceptibility. Very little is known about the shaping of T cell repertoire towards self antigens in humans and their contribution to disease susceptibility in autoimmune disorders. Here we report the comparative T cell epitope recognition patterns towards the MBP auto-antigen in healthy identical twins. We have established MBP-specific T cell lines from eight sets of twins and characterized their fine epitope specificity. Intra-pair comparison showed the co-existence of shared as well as distinct epitopes in six of eight pairs and a complete absence of concordant epitope recognition within two other pairs. These findings indicate that important differences in T cell repertoires against a self antigen may be observed between genetically identical healthy individuals, rendering difficult the interpretation of the differences which may be observed between identical twins discordant for an autoimmune disease.     

Typical patterns in atypical anorexia nervosa

Only a few published accounts describe atypical anorexia nervosa. To provide more information about this eating-disorder subtype, 15 patients (12 females, 3 males) with atypical anorexia nervosa were studied. In general, the 12 female patients were characterized by 1) older age at onset and presentation, 2) recurring bouts of depression, 3) numerous somatic complaints, 4) unmet dependency needs, and 5) little evidence of distortion in body image. The three male patients were characterized by a younger age at onset compared to the females, and in many ways they resembled young female anorexics or bulimic anorexics.     

The Eating Attitudes Test: an index of the symptoms of anorexia nervosa.

Data on the development of a 40-item measure of the symptoms in anorexia nervosa are reported. The scale (EAT) is presented in a 6-point, forced choice, self-report format which is easily administered and scored. The EAT was validated using 2 groups of female anorexia nervosa patients (N = 32 and 33) and female control subjects (N = 34 and 59). Total EAT score was significantly correlated with criterion group membership (r = 0.87, P less than 0.001), suggesting a high level of concurrent validity. There was very little overlap in the frequency distributions of the 2 groups and only 7% of the normal controls scored as high as the lowest anorexic patient. Female obese and male subjects also scored significantly lower on the EAT than anorexics. Recovered anorexic patients scored in the normal range on the test, suggesting that the EAT is sensitive to clinical remission.     

Down''s syndrome in twins

Male twins concordant for Down's syndrome and female twins discordant for Down's syndrome were investigated. Both males have trisomy 21 (47, XY, 21 +), and their parents are normal. One of the female twins is mosaic for trisomy 21 (46, XX/47, XX, 21 +) and the other is normal (46, XX). On the basis of multiple parameters, it is suggested that both pairs of twins are mono-zygous, including the female twins discordant for Down's syndrome.
Once the underlying cytogenetic mechanisms are understood and elucidated, genetic counselling can be undertaken.     

Timing of de novo mutagenesis--a twin study of sodium-channel mutations

De novo mutations are a cause of sporadic disease, but little is known about the developmental timing of such mutations. We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy. On the basis of our findings and the literature on mosaic cases, we conclude that de novo mutations in SCN1A may occur at any time, from the premorula stage of the embryo (causing disease in the subject) to adulthood (with mutations in the germ-line cells of parents causing disease in offspring).     

P300 amplitude in adolescent twins discordant and concordant for alcohol use disorders

The sons of alcoholics have repeatedly been found to have reduced P300 amplitude. Further, quantitative behavioral genetic and molecular genetic studies indicating a genetic influence on P300 amplitude have fueled speculation that this component may be a biological vulnerability marker for alcoholism. To further explore this possibility, we examined P300 in adolescent twin pairs from an epidemiological sample who were (a) discordant for alcohol abuse/dependence, (b) concordant for alcohol abuse/dependence, or (c) concordant for the absence of alcohol abuse/dependence and other relevant disorders. For discordant pairs, the alcohol abusing/dependent twins' amplitude did not differ from that of non-alcoholic co-twins. Pairs free of psychopathology had greater amplitudes than both alcoholism discordant and concordant pairs. P300 amplitude was more similar in monozygotic than dizygotic discordant pairs, suggesting a genetic influence on P300 amplitude in this group. The findings are consistent with P300 amplitude being a marker of vulnerability to alcohol use disorders.     

Hypothalamic-pituitary-thyroidal dysfunctions in anorexia nervosa

There are clinical similarities between anorexia nervosa and hypothyroidism. Circulating levels of T4 and particularly T3 have been reported to be low in this eating disorder. Previous reports have, however, shown normal basal levels of serum TSH with normal or delayed responses to TRH. To assess thyroid function and the hypothalamic-pituitary axis in 21 women with anorexia nervosa, serum levels of free and total thyroid hormones, binding proteins, and TSH employing an extremely sensitive assay (detection limit = 0.02 microU/ml) were measured. Serum T4, free T4, T3, free T3, TSH, TBG and TBPA concentrations were significantly lower and rT3 levels were significantly higher in anorexia nervosa patients than in normal controls. A delayed TSH response to TRH was noted in 66% of patients, hyporesponsiveness was seen in another 24%, and a normal response in only 10%. In 10 anorexia nervosa patients studied after weight gain, T4, T3, free T3, TSH, TBG and TBPA were significantly increased, and rT3 was significantly decreased. No change in mean free T4 levels with weight gain was noted. Other parameters of hypothalamic dysfunction in anorexia nervosa have been reported and the present data suggest that apparent hypothalamic hypothyroidism occurs perhaps as an adaptation to prolonged starvation.     

Feeding conditions and estrous cycle of female rats under the activity-stress procedure from aspects of anorexia nervosa.

The present study investigated the application of female rats with activity stress as an animal model for anorexia nervosa. Young female rats were singly housed in activity-wheel cages with food-restricted schedule (2, 3, or 4 h of food availability per day) for 3 weeks. Estrous cycle, body weight, food intake, and wheel revolution were recorded daily. Gastric pathology was also observed using the endoscopic technique. Rats that were subjected to either a 3- or 4-h feeding schedule exhibited the cessation of estrous cycle, loss of body weight, and suppression of food intake. These animals also showed a remarkable increase in running activity. However, they had no gastric lesions throughout the experimental period. On the contrary, the 2-h feeding schedule elicited severe gastric lesions and high mortality. The results suggest that behavioral and physiological changes of the young female rats with 3 or 4 h feeding share some symptoms of anorexia nervosa, although their anorexia is not self starvation.     

Phenylthiocarbamide tasting in a sample of twins

1. Twenty-eight pairs of monozygotic and eighteen pairs of dizygotic twins were tested for their ability to taste phenylthiocarbamide (P.T.C.) by the method of Harris & Kalmus (1949). 2. Much greater variance in threshold levels was detected within the DZ than within the MZ pairs and this confirms the genetic origin of most variation in ability to taste this substance. 3. Variance in threshold levels within MZ pairs is of the same magnitude as the variance of reported duplicate measurements on the same individuals. 4. DZ twin pairs were classified as either concordant or discordant in their tasting ability. Variance within concordant DZ pairs is significantly greater than within the MZ pairs and it is shown that this difference can be accounted for in terms of the incomplete dominance of the T allele reported by Kalmus (1958). However, the data do not exclude the possiblity that this greater variation in threshold levels is partly due to multiple alleles or background genetic variation. 5. The frequency of the t allele in Australians of European descent in estimate at 0-52 plus or minus 0-06.     

Symptomatology, psychosexual development and gender identity in 42 anorexic males

Forty-two male patients with an anorexic syndrome were assessed. Twenty-nine of them had a primary anorexia nervosa (most of them also had bulimic symptoms). They were compared with a series of 23 female anorexia nervosa patients. The males scored more highly than female patients on a number of symptoms, but generally more similarities than differences in symptomatology were apparent. Male patients with primary anorexia nervosa also showed several signs of a disturbed psychosexual and gender identity development. The data support the hypothesis that males with atypical gender role behaviour have an increased risk for developing anorexia nervosa or bulimia in adolescence.     

A preliminary population-based twin study of self-reported eating disorder

BACKGROUND: Twin studies have concluded that there is a substantial genetic contribution to the aetiology of eating disorders. The aim of the present study was to estimate the genetic contribution to the aetiology of self-reported eating disorders in a sample of representative twins. METHOD: A population cohort of 34142 young Danish twins was screened for eating disorders by a mailed questionnaire. RESULTS: Concordance rates differed significantly across monozygotic and dizygotic twin pairs for broadly defined self-reported anorexia nervosa and bulimia nervosa. Heritability estimates of 0.48, 0.52 and 0.61 respectively were estimated for narrow and broad definitions of self-reported anorexia nervosa and for self-reported bulimia nervosa. CONCLUSIONS: There is a genetic contribution to the aetiology of self-reported eating disorders in the general population. The relationship between self-reported and clinical eating disorder remains to be examined.     

Apolipoprotein E type ε4 allele, heritability and age at onset in twins with Alzheimer disease and vascular dementia

The apolipoprotein E (APOE) ε4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the ε4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the ε4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the ε4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The ε4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE ε4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in ε4 homozygotes than in individuals with one or no copies of ε4 (62.4 vs. 73.5, p < 0.01). In concordant AD twin pairs, the ε4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without ε4 in their genotypes.     

What predicts suicide attempts in women with eating disorders?

BACKGROUND: Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. METHOD: In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. RESULTS: Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1%) than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. CONCLUSIONS: Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity.