On prepulse inhibition of the acoustic startle response and the influence of methylphenidate in children with attention-deficit/hyperactivity disorder

Abstract

In addition to numerous symptoms, an interesting observation in AD(H)D is that it is frequently associated with monosymptomatic enuresis (Ornitz et al. 1992). The pathophysiology of monosymptomatic enuresis, like that of AD(H)D, is still not fully understood (Sumner et al. 2006).

Studies in children with enuresis have demonstrated reduced reflex inhibition (prepulse inhibition [PPI]) in startle experiments; this reduction was even more pronounced when AD(H)D was also present, but was not detectable in AD(H)D without enuresis (Ornitz et al. 1999). Measurement of PPI of the acoustic startle response is an established method for assessing mechanisms of so-called “sensorimotor gating” (Feifel et al. 2009). Sensorimotor gating is a central reflex-control mechanism at the brainstem level that distinguishes meaningless from meaningful information, filters it out, and thereby suppresses it. In this way, only important information is processed in the brain (Schwabe et al. 2009). For example, the acoustic information from an airplane flying past will not affect an ongoing activity such as riding a bicycle. In children with AD(H)D, precisely this function appears to be deficient, because these children seem unable to distinguish between “important” and “unimportant” information. A child with AD(H)D could, for example, be so distracted by the airplane that the child can no longer concentrate on riding the bicycle.

PPI is part of a maturation process that is delayed in various disorders (Feifel et al. 2009). In children with enuresis, dDAVP therapy (1-desamino-8-D-arginine vasopressin) produced an improvement in PPI (Schulz-Juergensen et al. 2007). Some patients have both enuresis and AD(H)D, and interestingly the AD(H)D symptoms also improve during dDAVP therapy (S. Schulz-Juergensen, personal communication). Conversely, treatment of AD(H)D has been observed to reduce the symptoms of monosymptomatic enuresis (Shatkin 2004). This suggests that there may be commonalities in the pathogenesis of AD(H)D and monosymptomatic enuresis. This raises the question of whether pharmacological treatment with methylphenidate might also improve PPI in children with AD(H)D, or at least in a subgroup of them, and thus provide a better understanding of the mechanisms of action of this medication. This dissertation therefore tests the hypothesis that methylphenidate therapy influences PPI in children with AD(H)D, or in at least part of this group. Confirmation of this hypothesis would have implications for understanding the disorder and its treatment.