tourette

mise à jour du 1 novembre 2014 Front Psychol 2014	Tourette-like behaviors in the normal population are associated with hyperactive/impulsive ADHD-like behaviors but do not relate to deficits in conditioned inhibition or response inhibition Heym N, Kantini E, Checkley HL, Cassaday HJ. School of Psychology, University of Nottingham, Nottingham, UK
Abstract Attention-Deficit Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) present as distinct conditions clinically; however, comorbidity and inhibitory control deficits have been proposed for both. Whilst such deficits have been studied widely within clinical populations, findings are mixed—partly due to comorbidity and/or medication effects—and studies have rarely distinguished between subtypes of the disorders. Studies in the general population are sparse. Using a continuity approach, the present study examined (i) the relationships between inattentive and hyperactive/impulsive aspects of ADHD and TS-like behaviors in the general population, and (ii) their unique associations with automatic and executive inhibitory control, as well as (iii) yawning (a proposed behavioral model of TS). One hundred and thirty-eight participants completed self-report measures for ADHD and TS-like behaviors as well as yawning, and a conditioned inhibition task to assess automatic inhibition. A sub-sample of fifty-four participants completed three executive inhibition tasks. An exploratory factor analysis of the TS behavior checklist supported a distinction between phonic and motor like pure TS behaviors. Whilst hyperactive/impulsive aspects of ADHD were associated with increased pure and compulsive TS-like behaviors, inattention in isolation was related to reduced obsessive-compulsive TS-like behaviors. TS-like behaviors were associated with yawning during situations of inactivity, and specifically motor TS was related to yawning during stress. Phonic TS and inattention aspects of ADHD were associated with yawning during concentration/activity. Whilst executive interference control deficits were linked to hyperactive/impulsive ADHD-like behaviors, this was not the case for inattentive ADHD or TS-like behaviors, which instead related to increased performance on some measures. No associations were observed for automatic conditioned inhibition. Introduction Attention-Deficit/Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) present as distinct conditions clinically; however, there is evidence of comorbidity between those two disorders and inhibitory control deficits have been proposed for both (Eddy et al., 2009). ADHD is a neurodevelopmental disorder characterized by excessive inattention, hyperactivity and impulsivity, and diagnosis typically comprises three subtypes for inattentive, hyperactive/impulsive, or combined ADHD cases. ADHD has predominantly been studied using clinical populations of children and/or adults, and this research suggests that the psychological symptoms of ADHD derive from deficient inhibitory control (Barkley, 1997; Quay, 1997; Ozonoff et al., 1998). As the symptoms and behaviors have been suggested to be dimensional with extreme manifestations leading to diagnosis (Coghill and Sonuga-Barke, 2012), research has also begun to examine individual differences in ADHD-like behaviors and their links to response inhibition in the general population (Kuntsi et al., 2005; Herrmann et al., 2009). TS is also a neurodevelopmental hyperkinetic disorder, in this case involving sudden, repetitive unintentional movement-based tics (motor tics) and involuntary sounds or utterances produced by moving air through the nose, mouth, or throat (phonic tics). Phonic and motor tics relate to separate diagnostic criteria as they involve discrete muscle groups, and phonic tics are generally more common (Leckman et al., 2006). Factor analytic studies (Khalifa and Knorring, 2005; Robertson et al., 2008) have shown that there are pure or uncomplicated (without comorbidity, prevalent in 10% of patients) and comorbid phenotypic expressions of TS, mainly associated with ADHD and obsessive-compulsive disorder (OCD) (Bloch and Leckman, 2009; Cavanna et al., 2009). Consequently, many clinical studies include patients with symptoms of ADHD or OCD. Attentional and impulse control problems are thought to precede the emergence of TS symptoms, and it is the behavioral disturbances and impaired executive functioning typical of ADHD that appear to be most closely linked to TS (for review see Robertson, 2000). The obsessive-compulsive behaviors (OCBs) most characteristic of TS appear to be clinically different from those seen in pure OCD, and involve repetitive thoughts of aversive content, and compulsions to do with checking, sorting and arranging (Robertson, 2000). TS has been linked to cognitive and executive functioning impairment, however, the specificity of these deficits to pure TS as opposed to comorbid conditions is less clear (Eddy et al., 2009). Moreover, as TS-like behaviors involve separate behavioral aspects (phonic and motor), these may show differential associations with the subtypes of ADHD, OCBs, and response inhibition deficits. Whilst research has begun to examine individual differences in ADHD-like behaviors in the general population, this is not the case for TS. However, it is recognized that TS lies at the extreme of what can be viewed as a tic disorder spectrum which includes also “transient,” “chronic,” and “non-specific” tic disorders (Leckman, 2002). Therefore, the main aim of this study is to examine individual differences in the general population in the expression of behaviors similar to those seen in TS and ADHD and their links to response inhibition. Inhibition is a broad but nonetheless useful construct, particularly in relation to the deficits characteristic of a range of psychopathologies. Based on an extensive review, Nigg (2000) proposed an integrated taxonomy of inhibition in which inhibitory control (broadly defined) includes executive, automatic and motivational inhibitory processes, each corresponding to separate cognitive, personality and neural underpinnings. Differentiating amongst these allows more systematic identification of the specific inhibitory control mechanisms linked to various psychopathologies (Nigg, 2000). In the case of ADHD and TS, the most widely studied inhibitory processes fall under the class of effortful executive inhibition. This includes interference control of motor or cognitive responses due to resource or stimulus competition—typically assessed by tasks which require respondents to suppress (their perception of) a stimulus and competing response in order to execute the primary response, such as in the standard Stroop or Flanker tasks. Similarly, behavioral inhibition requires suppressing a dominant or pre-potent automatic response option—typically assessed with the Go/No-Go or Stop-Signal tasks. A variety of studies using these tasks, have demonstrated deficits in executive response inhibition in children and adults with ADHD (Schachar and Logan, 1990; Iaboni et al., 1995; Seidman et al., 1997; Konrad et al., 2000; Schachar et al., 2000; Young et al., 2006). A meta-analysis suggested slower go and stop reaction times in ADHD children; however, this was non-specific in that children with conduct disorder showed similar deficits (Oosterlaan et al., 1998). Importantly, though a number of studies report executive inhibition deficits in ADHD, comorbidity was not accounted for in most, and those studies that did, typically found that deficits are not necessarily specific to ADHD. Indeed, a more recent meta-analysis of executive dysfunction in clinic-referred and community ADHD samples (across 83 studies) found only moderate effect sizes, consistent with the lack of universality of these deficits (Willcutt et al., 2005). Similar to ADHD, it has been argued that TS may be a result of an inhibitory dysfunction (Sheppard et al., 1999). While some studies have found inhibitory deficits (Georgiou et al., 1995; Marsh et al., 2004; Crawford et al., 2005), the overall evidence of inhibitory impairment in TS is inconsistent, and has similarly been attributed to comorbidity issues (Pennington and Ozonoff, 1996). Indeed, a number of studies report no significant difference in cognitive and behavioral executive response inhibition between TS groups without comorbid ADHD and matched controls. For example, participants with pure TS showed no performance deficits on Go/No-Go (Serrien et al., 2005; Roessner et al., 2008), color-word Stroop or Flanker tasks (Channon et al., 2003, 2006, 2009). Similarly, Ozonoff et al. (1998) found normal inhibition effects in children with mild TS but impaired inhibition in children with TS and comorbid ADHD or OCD. Thus, it has been suggested that ADHD comorbidity may contribute to, or possibly be responsible for the inhibitory deficits observed in TS (Ozonoff et al., 1998; Como, 2001; Channon et al., 2003; Gilbert et al., 2004; Eddy et al., 2009). Indeed, Jackson and colleagues have shown that, despite their general difficulties with inhibition, pure TS participants (without comorbidity) show paradoxically enhanced volitional control in suppressing established learned associations, in both saccadic and manual switching tasks (Mueller et al., 2006; Jackson et al., 2007, 2011a; Jung et al., 2014). Such tasks rely on executive processes to show the required flexibility when the response requirement is changed. Thus, the above studies of inhibitory (dys)function have used volitional response measures involving conscious control, which can be classified as effortful executive inhibition category (Nigg, 2000). To date, little research has examined motivational or automatic inhibitory processes in ADHD and TS, though clinical studies suggest that automatic attentional inhibition may be of particular importance in the inattentive subtype of ADHD (Aman et al., 1998). To gain specificity regarding unique deficits in different psychopathologies, the ideal approach is to simultaneously examine and distinguish different types of response inhibition deficits using several response inhibition tasks and in more than one disorder, whilst controlling for comorbidity (Nigg, 2000). From a learning theory perspective, successful performance on such tasks detailed above requires inhibition of pre-potent stimulus-response (S-R) associations. The learning of stimulus-stimulus (S-S) associations follows the general laws of associative learning and may well rely on similar mechanisms, however, there are differences in the specific neural circuitries involved depending on the type of S-R (Jog et al., 1999; Killcross and Coutureau, 2003; Yin and Knowlton, 2006) or S-S conditioning procedure in use (Daum et al., 1993; Fanselow and Poulos, 2005; Kim and Jung, 2006). Given that different neural circuitries are necessary for S-R and S-S associations, we cannot assume that both types of learning are affected in ADHD or TS. Indeed, when performance on procedural (S-R) learning tasks was systematically compared with tasks requiring associative learning (based on S-S as well as S-R associations) in TS patients, the underlying learning systems were suggested to be dissociable (Marsh et al., 2005). However, there have been few reported studies of S-S learning and the role of automatic inhibition in ADHD or TS. Studies using inhibition of return have found no evidence for such inhibitory deficits in cases of TS without comorbidity (Yuen et al., 2005). Similarly, negative priming, though impaired in OCD, appears to be spared in TS and adult ADHD (Ozonoff et al., 1998; Nigg et al., 2002). A latent inhibition study—in which stimulus pre-exposure attenuates later S-S learning—found also no deficit in TS participants (Swerdlow et al., 1996). However, although latent inhibition procedures effectively inhibit the acquisition of a new association, they do not render the pre-exposed stimulus truly inhibitory (Baker and Mackintosh, 1977). True inhibition is demonstrated by establishing a stimulus selectively to predict the occasions on which an otherwise expected outcome will not occur (Pavlov, 1927; Rescorla, 1969), as seen in conditioned inhibition (CI) procedures. Thus, the inhibition of S-S associations (termed conditioned inhibition) has been defined in terms of the learned ability of a stimulus to inhibit an earlier established association (Rescorla, 1969). More specifically, the presence (during an excitatory association) of a stimulus which signals the absence of the otherwise expected event, establishes the additional stimulus as inhibitory (Pavlov, 1927). Since CI can be established in both implicit and explicit learning variants, it should be classified as automatic rather than effortful inhibition. CI has only recently been examined in clinically diagnosed children and adolescents with ADHD (Kantini et al., 2011a) and TS in the absence of comorbid ADHD (Kantini et al., 2011b). Although there was no evidence for any differences in CI between ADHD or TS groups compared to matched controls, in both disorders performance was dependent on medication. In ADHD participants, both higher dosage and longer duration of treatment with methylphenidate were related to improved CI when symptom severity was taken into account (Kantini et al., 2011a). On the other hand, medication with clonidine for TS impaired CI (Kantini et al., 2011b). Thus, differences in CI in ADHD and TS were related to medication rather than diagnosis. Hence, previous studies conducted in clinically diagnosed and treated populations may be limited to the extent that observed performance differences may be confounded by medication status as well as comorbidity. Moreover, given the difficulties in recuiting pure cases (without comorbidity), the majority of experimental studies conducted in clinical populations have looked at ADHD without differentiating between hyperactive/impulsive and inattentive subtypes of the disorder. Establishing differential performance deficits based on behavioral subtypes of either ADHD or TS may be also key to the delineation of their respective deficits. To date a relatively small number of studies have addressed the relationship between inhibition deficits and subtypes of ADHD. Willcutt et al.'s (2005) meta-analysis in clinical samples supports executive performance deficits in combined and inattentive ADHD subtypes, whereas impairment in the hyperactive/impulsive subtype was minimal (though only three studies included the latter). Herrmann et al. (2009) found executive response inhibition deficits for inattentive but not hyperactive/impulsive ADHD-like behaviors in a healthy non-clinical adult sample. Thus, the subtypes of ADHD appear to be differentially related to response inhibition deficits, but further evidence is needed. Whilst recent studies began to examine executive response inhibition deficits linked to subtypes of ADHD-like behaviors in the clinical and general population, to date there are no studies that have been applied to TS-like behaviors in a similar way. Moreover, whilst automatic attentional inhibition has been suggested to be of particular importance in the inattentive subtype of ADHD (Aman et al., 1998), there are no studies that have examined the association of the subtypes of ADHD with automatic inhibition deficits in the general population. Therefore, following a dimensional approach, the main aim of the current study was to examine (i) the associations between the different behavioral aspects of both conditions in the general population, and (ii) their unique roles in inhibitory control deficits, specifically in automatic inhibition. Few studies have used various tasks of response inhibition simultaneously to assess disorder and subtype specificity of deficits (Nigg, 2000), and indeed, none has explicitly compared performance on standard response inhibition tasks and CI of S-S associations in the normal population. Therefore, extending the experimental approaches previously adopted in the ADHD and TS literature, the current study set out to examine automatic response inhibition deficits related to the subtypes of TS- and ADHD-like behaviors in the general population and compare those to executive response deficits in a subsample. Whilst there are established ADHD scales for use in normal populations (ASRS; Kessler et al., 2005), that differentiate between hyperactive/impulsive and inattentive behaviors, currently there are no such scales to measure TS-like behaviors in normal populations. Therefore, we developed a short behavioral checklist similar in format to the ASRS tapping into the different behavioral aspects of TS (including pure motor and phonic tic related behaviors, as well as OCBs) in order to examine the overlap between TS-like behaviors with ADHD subtypes and their associations with automatic and effortful response inhibition deficits. Moreover, tics can be triggered by various situations and are often preceded by premonitory sensations (Prado et al., 2008), which may become tic-generating stimuli through S-S associations (Robertson, 2000). For example, whilst tics can be temporarily suppressed using distraction, they appear to increase during stress and relaxation after stress (Jankovic, 1997). Yawning is a stereotyped repetitive motor act occurring during such situations, increasing arousal and self-awareness, and it has been suggested that excessive yawning is associated with and triggering TS tics (Dalsgaard et al., 2001; Walusinski et al., 2010). Both, yawning and TS (like a number of other bodily sensations) have been conceptualized as “urges for action,” and based on the overlap in the functional anatomy, yawning has been proposed as a behavioral model for TS (Jackson et al., 2011b). It has been suggested that identifying premonitory sensations and subjective experiences associated with symptom expression may be useful in identifying more homogenous subgroups of TS (Prado et al., 2008). Therefore, we also included a scale assessing yawning in different contexts (Greco and Baenninger, 1993) to examine its associations with different TS-like behaviors. The hypotheses tested were as follows: (i) based on comorbidity in clinical groups, ADHD- and TS-like behaviors were predicted to be positively associated; (ii) in line with the notion of the behavioral yawning model for TS, TS-like behaviors were predicted to be associated with excessive yawning also in contexts unrelated to fatigue or boredom; (iii) automatic attentional inhibition deficits were expected only in relation to the inattentive ADHD subscale (Aman et al., 1998); (iv) controlling for “comorbidity,” ADHD-like behaviors were predicted to be more strongly associated with deficits in tasks measuring executive inhibitory control; whereas any apparent relationships with TS-like behaviors are due to ADHD-like behaviors or OCBs known to co-occur with TS. Go to: Materials and methods ------ Yawning as a behavioral model of TS Analysis of the Yawning scale yielded a three factor solution distinguishing between active, inactive and stress induced yawning. The Yawning scales were significantly positively correlated with pure (and overall) TS-like behaviors, and YWN-inactive was also associated with compulsive TS behaviors. The Yawning scales also showed some associations with ADHD-like behaviors, whereby YWN-activity (and overall) was significantly positively associated with all ASRS scales, and YWN-inactivity with hyperactive/impulsive (and overall) ASRS. However, YWN-stress was not linked to ASRS. The regression analyses for the unique contribution of the TS and ASRS scales (thus accounting for covariation amongst those) showed that only the three TS-like behaviors remained significantly associated with yawning during inactivity, and only motor TS-like behaviors with yawning during stressful situations involving self-presentation/awareness. The ASRS scales were not linked to these two yawning scales. In contrast, only phonic (but not motor or OCB) TS-like behaviors and inattentive (but not hyperactive/impulsive) ASRS were positively associated with yawning during activity involving concentration. In general, the findings support the notion that excessive yawning is associated with TS (Dalsgaard et al., 2001; Walusinski et al., 2010), but suggest that the behavioral yawning model may be more specific to TS in the context of relaxation (for all TS behaviors) or during self-awareness and stress (specifically for motor tics). Secondly, phonic tics, characterized by involuntary sounds produced by moving air through the nose, mouth, or throat, and underlying the same muscle groups as yawning itself (Leckman et al., 2006), are linked to yawning across different everyday situational contexts (inactive and active). Given the role of premonitory sensations in tic-generating S-S associations (Robertson, 2000), this suggests that yawning in those situations may trigger more common phonic tics. Yawning during stressful situations involving greater self-awareness, however, may be more likely to trigger motor tics, which also involve different muscle groups (Leckman et al., 2006). Thus, taking the situational context of premonitory sensations associated with different symptom expression into account may be useful in studying homogenous subgroups of TS (Prado et al., 2008). However, the finding that ASRS-inattention was associated with yawning during activity suggests that the behavioral yawning model may also be useful for ADD, and warrants further investigation in clinical samples. Given that yawning is thought to increase arousal (Walusinski et al., 2010), it may well be a functional response to increase attention during situations where concentration is required.