Effect of co-twin gender on neurodevelopmental symptoms: a twin register study

Eriksson, Jonna; Lundström, Staffan; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

doi:10.1186/s13229-016-0074-z

Cited by 17 publications

(24 citation statements)

References 51 publications

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“…A recent Swedish investigation suggested that merely having a female cotwin is associated with displaying a greater degree of ADHD traits than having a male cotwin, although this study did not take account of the degree to which the index twin displayed ADHD symptoms. 13 In 1 study of a US-based twin sample, traits of ADHD were examined in the cotwins of individuals displaying a high degree of traits of ADHD. Cotwins of females displaying extreme ADHD traits displayed significantly greater ADHD-like behaviors than cotwins of males displaying extreme traits of ADHD.…”

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confidence: 99%

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Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Taylor

Lichtenstein

Larsson

et al. 2016

Journal of the American Academy of Child & Adolescent Psych

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ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is more frequent in males than in females. The “female protective effect” posits that females undergo greater exposure to etiological factors than males in order to develop ADHD, leading to the prediction that relatives of females with ADHD will display more ADHD behaviors. We thus tested whether cotwins of females displaying extreme ADHD traits would display more ADHD traits than cotwins of males displaying extreme ADHD traits.MethodParents of approximately 7,000 pairs of nonidentical twins in Sweden, and approximately 4,000 pairs of twins in England and Wales, completed dimensional assessments of ADHD traits. Probands were selected on the basis of scoring within the highest 10% of the distribution in each sample. Dimensional scores of cotwins of probands, as well as the categorical recurrence rate, were investigated by proband sex.ResultsCotwins of female probands displayed higher mean ADHD trait scores (mean = 0.62−0.79) than cotwins of male probands (mean = 0.38−0.55) in both samples. This trend was significant in the Swedish sample (p < .01) and when the 2 samples were merged into a single, larger sample (p < .001). When the samples were merged, there was also a significant association between proband sex and cotwin’s categorical status, with more cotwins of female probands also being probands than cotwins of male probands.ConclusionThese findings support a female protective effect against ADHD behaviors, suggesting that females require greater exposure to genetic and environmental factors associated with ADHD in order to develop the condition.

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confidence: 99%

“…We expected, in light of existing evidence, to find evidence of a female protective effect against ADHD behaviors. 13 , 14 …”

mentioning

confidence: 99%

Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Taylor

Lichtenstein

Larsson

et al. 2016

Journal of the American Academy of Child & Adolescent Psych

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“…As far as we know, no previous studies have compared the risk of epilepsy in OS and SS twins. Findings for attention deficit hyperactivity disorder (ADHD) and autism are conflicting [ 33 – 35 ]. Higher levels of testosterone in amniotic fluid have been associated with autism in some [ 32 ], but not all studies [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, a study showed the SS male twins had a higher risk of autism compared with OS male twins [ 33 ]. Other studies, however, did not support the TTT hypothesis [ 34 , 35 ]. Instead, the studies found that girls with a male co-twin had less ADHD and autistic traits than girls with a female co-twin [ 34 , 35 ] indicating the complexity of the effect of fetal hormones on brain development.…”

Section: Introductionmentioning

confidence: 94%

“…Other studies, however, did not support the TTT hypothesis [ 34 , 35 ]. Instead, the studies found that girls with a male co-twin had less ADHD and autistic traits than girls with a female co-twin [ 34 , 35 ] indicating the complexity of the effect of fetal hormones on brain development. The interaction between sex hormones and epilepsy is complex [ 36 ].…”

Section: Introductionmentioning

confidence: 94%

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Risk of epilepsy in opposite-sex and same-sex twins: a twin cohort study

et al. 2018

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BackgroundThere is a complex interaction between female and male sex hormones and the risk of epilepsy. Whether prenatal exposure to higher levels of sex hormones affects the development of epilepsy in childhood or later in life is not well known. The sex hormone environment of fetuses may be affected by the sex of the co-twin. We estimated the risk of epilepsy for twins with an opposite-sex (OS) co-twin compared with twins with a same-sex (SS) co-twin.MethodsFrom the Danish Twin Registry, we identified OS female twins (n = 11,078), SS female twins (n = 19,186), OS male twins (n = 11,080), and SS male twins (n = 20,207) born between 1977 and 2009. The SS twins include monozygotic twins, dizygotic twins, and twins with unknown zygosity. These children were followed up from day 29 after birth until diagnosis of epilepsy, death, emigration, or end of follow-up (31 December 2011) whichever came first. Information on diagnosis of epilepsy was obtained from the Danish National Patient Registry. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for epilepsy in the OS twins using a Cox proportional hazards regression model compared with the SS twins. To account for the correlation of twins from the same mother when estimating standard errors, we used the cluster option in Stata.ResultsWe identified 152 OS female twins, 282 SS female twins, 162 OS male twins, and 335 SS male twins diagnosed with epilepsy corresponding to an incidence rate of 9.9 and 9.7 per 10,000 person years for the OS and SS female twins, and 10.6 and 10.9 per 10,000 person years for the OS and SS male twins, respectively. We found a similar risk of epilepsy among the OS and SS female twins [HR = 1.01; 95% CI 0.83–1.24] as well as among the OS and SS male twins [HR = 0.94; 95% CI 0.78–1.14]ConclusionsIn this population-based study of Danish twins, we did not find difference in the risk of epilepsy between twins with an OS co-twin and twins with a SS co-twin. This applied to both female and male twins. The study therefore does not support the hypothesis that subtle hormone difference in fetal life due to co-twin may play a role in the development of epilepsy later in life.

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Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study

Deng

Wang

2021

Autism Research

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Autism spectrum disorder (ASD) is diagnosed much more often in males than females. This male predominance has prompted a number of studies to examine how sex differences are related to the neural expression of ASD. Different theories, such as the “extreme male brain” theory, the “female protective effect” (FPE) theory, and the gender incoherence (GI) theory, provide different explanations for the mixed findings of sex‐related neural expression of ASD. This study sought to clarify whether either theory applies to the brain structure in individuals with ASD by analyzing a selective high‐quality data subset from an open data resource (Autism Brain Imaging Data Exchange I and II) including 35 males/35 females with ASD and 86 male/86 female typical‐controls (TCs). We examined the sex‐related changes in ASD in gray matter asymmetry measures (i.e., asymmetry index, AI) derived from voxel‐based morphometry using a 2 (diagnosis: ASD vs. TC) × 2 (sex: female vs. male) factorial design. A diagnosis‐by‐sex interaction effect was identified in the planum temporale/Heschl's gyrus: (i) compared to females, males exhibited decreased AI (indicating more leftward brain asymmetry) in the TC group, whereas AI was greater (indicating less leftward brain asymmetry) for males than for females in the ASD group; and (ii) females with ASD showed reduced AI (indicating more leftward brain asymmetry) compared to female TCs, whereas there were no differences between ASDs and TCs in the male group. This interaction pattern supports the FPE theory in showing greater brain structure changes (masculinization) in females with ASD. Lay Summary To understand the neural mechanisms underlying male predominance in autism spectrum disorder (ASD), we investigated the sex differences in ASD‐related alterations in brain asymmetry. We found greater changes in females with ASD compared with males with ASD, revealing a female protective effect. These findings provide novel insights into the neurobiology of sex differences in ASD.

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Effect of co-twin gender on neurodevelopmental symptoms: a twin register study

Cited by 17 publications

References 51 publications

Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples

Risk of epilepsy in opposite-sex and same-sex twins: a twin cohort study

Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study

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