169 EF and Local-global visual processing in ASD relatives

4.3. Concluding remarks and future directions

Overall, we found that ASD relatives displayed impairments on tasks TLHZ\YPUN YLZWVUZL PUOPIP[PVU JVNUP[P]L ÅL_PIPSP[` HUK NLULYH[P]P[` ^P[O NLULYH[P]P[`KLÄJP[ZILPUN[OLTVZ[WYVUV\UJLK(KKP[PVUHSS`,-PTWHPYTLU[Z in daily life were reported. Regarding local-global visual processing, no group KPɈLYLUJLZ^LYLMV\UKVUHU`VM[OL[HZRZI\[(:+YLSH[P]LZKPKZOV^TVYL H[[LU[PVU[VKL[HPSPUKHPS`SPML;OLZLNYV\WKPɈLYLUJLZ^LYLLX\HSS`WYVUV\UJLK for siblings and parents of probands with ASD. Furthermore, when comparing [OLT\S[PWSL_HUK[OLM\SSZHTWSL^LKPKÄUKSHYNLYLɈLJ[ZPaLZMVY[OLT\S[PWSL_ ZHTWSL I\[ UV HKKP[PVUHS NYV\W KPɈLYLUJLZ LTLYNLK WYVIHIS` K\L [V [OL smaller sample size.

However, the results of the full and the multiplex sample might not be KPYLJ[S` JVTWHYHISL NP]LU [OL SHYNL HNL KPɈLYLUJLZ IL[^LLU IV[O ZHTWSLZ The full sample contains both children and adults, while the multiplex sample VUS`JVTWYPZLZHK\S[Z(S[OV\NO^LKLTVUZ[YH[LK[OH[[OLLɈLJ[VMNYV\WKPK UV[KPɈLYIL[^LLUJOPSKYLUHUKHK\S[ZUV.YV\W_(NLPU[LYHJ[PVUZ^LYLMV\UK ^LKPKÄUKSHYNLHNLLɈLJ[Z^P[OJOPSKYLUNLULYHSS`WLYMVYTPUNSLZZ^LSS[OHU HK\S[ZYLÅLJ[PUNSLZZZ[YVUNS`KL]LSVWLKJVNUP[P]LHIPSP[PLZPUJOPSKYLU.P]LU [OL SHYNLY HNL YHUNL PU [OL M\SS ZHTWSL [OLZL HNL LɈLJ[Z WYVIHIS` PUK\JLK TVYL]HYPHUJLHUK[O\ZTVYLUVPZL[VLS\JPKH[LNYV\WKPɈLYLUJLZPU[OLM\SS compared to the multiplex sample. We did account for the age induced variance I`PUJS\KPUN[OLLɈLJ[VMHNLPU[OLTVKLSMVY[OLM\SSZHTWSL5L]LY[OLSLZZ[V KPYLJ[S`JVTWHYL[OLNYV\WKPɈLYLUJLZMVY[OLM\SSHUK[OLT\S[PWSL_ZHTWSLP[ would be better if both samples had a comparable mean age and age range.

(SS[OLVIZLY]LKNYV\WKPɈLYLUJLZJVYYLZWVUKLK^P[OWYL]PV\ZS`MV\UK KLÄJP[ZPU(:+WYVIHUKZZLL*OHW[LYZHUK;O\ZUVZ\WWVY[^HZWYV]PKLK for the suggestion by Johnson (2012) that EF could be a protective factor in ASD relatives enabling them to compensate for other atypicalities, since this implies better EF performance in ASD relatives than in TD controls. Additionally, ^L VIZLY]LK [OH[ [OL LɈLJ[ ZPaLZ VM [OL JVNUP[P]L H[`WPJHSP[PLZ PU [OL (:+ YLSH[P]LZ^LYLZTHSSLY[OHU[OVZLVM[OLZHTLKLÄJP[ZPU[OL(:+WYVIHUKZZLL Chapters 4 and 5). This is what one would expect for an ASD endophenotype. Not all relatives will share ASD risk genes with the proband, so at a group level JVNUP[P]LH[`WPJHSP[PLZ^PSSILSLZZWYVUV\UJLK/V^L]LY[OLZLÄUKPUNZKVUV[ necessarily imply that these cognitive characteristics of ASD relatives are good ASD endophenotypes. For example, it could be that these characteristics are not induced by an increased genetic liability in ASD relatives, but by detrimental environmental factors associated with having a child or sibling with ASD (e.g., more worries, stress, etc.). A good ASD endophenotype has to meet additional criteria (see Chapter 1: Introduction). These criteria will be evaluated in the next chapter (Chapter 7: General discussion).

(S[OV\NO^LMV\UKZPNUPÄJHU[NYV\WKPɈLYLUJLZ[OLLɈLJ[ZPaLZ^LYL small to medium. Furthermore, on most measures, ASD relatives performed comparably to TD individuals. In what follows, possible explanations for these ÄUKPUNZ^PSSILLSHIVYH[LKHUKZ\NNLZ[PVUZHYLTHKLMVYM\[\YLYLZLHYJO

170 EF and Local-global visual processing in ASD relatives

under study are not good ASD endophenotypes. However, it is also possible that several endophenotypic traits were not revealed in this study, because JLY[HPUJVNUP[P]LJOHYHJ[LYPZ[PJZ^LYLUV[L_WYLZZLKI`V\YZWLJPÄJZHTWSL of ASD relatives due to a number of reasons. For example, several ASD relatives in our study may not carry ASD risk genes, and thus not express the corresponding cognitive features, because the ASD characteristics in the proband are due to de novo mutations. In that case, one would expect that these mutations are transmitted to the next generation, indicating the importance of pedigree research and the inclusion of descendants of the ASD probands. Another possibility for the lack of cognitive impairments in ASD relatives is that they do share certain ASD risk genes, but that protective genetic and/or environmental factors prohibit their expression at a cognitive and/or behavioural level. These and other factors contribute to the large heterogeneity in the population of ASD relatives. Given the already large heterogeneity between ASD probands (Geurts, Sinzig, Booth, & Happé, 2014) and the fact that not all relatives share ASD risk genes with the probands, the variability is expected to be even larger in the ASD relatives population. This SHYNLOL[LYVNLULP[`L_WSHPUZ[OLZTHSS[VTLKP\TLɈLJ[ZPaLZHUK[OLTHU` PUJVUZPZ[LU[ÄUKPUNZIL[^LLUZ[\KPLZ[OH[MVJ\ZVUS`VUHZTHSSZ\IZHTWSL In other words, results could depend largely on the sample size and on the ZWLJPÄJZHTWSL[OH[PZPUJS\KLKPU[OLZ[\K`>LYLJY\P[LKZPISPUNZIL[^LLU and 18 years and parents between 30 en 60 years, all with a typical IQ (> 70), who had at least one ASD proband aged between 8 and 18 years old with an IQ above 70. In order to gain a really representative picture, future studies are needed comprising relatives of ASD probands spanning the whole age, 08HUK(:+ZWLJ[Y\T4VYLV]LYZ[\KPLZULLK[VILZ\ɉJPLU[S`SHYNL[VOH]L LUV\NOWV^LY[VKL[LJ[NYV\WKPɈLYLUJLZHUKWVZZPISLPU[LYHJ[PVUZ^P[O[OL type of relative (sibling vs. parent) and family status (simplex vs. multiplex). Acknowledgments

Lien Van Eylen was a doctoral and Bart Boets is a post-doctoral research fellow of the Research Foundation Flanders (FWO). Additionally, the research was funded by a fellowship from the Marguerite-Marie Delacroix Support Fund to Lien Van Eylen and a grant from the Research Council of KU Leuven to Jean Steyaert, Johan Wagemans, and Ilse Noens (IDO/08/013). We thank all participants for participating and all master students as well as Anouk Verhappen and Veerle Stevens for assistance in data collection and scoring.

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