Temperament Dimensions and Awakening Salivary Cortisol Levels in ADHD.

Università degli Studi di Sassari120 enrolled

Overview

To analyze heterogeneity in ADHD experts in last decade advised to look beyond the lists of existing symptoms towards phenotypic measures that can be represented dimensionally and have well-theorized relationships with neurobiological systems, (Sonuga-Barke \& Halperin, 2010; Insel et al, 2010; Fair D, Bathula D, Nikolas M, Nigg JT, 2012; Georgiades S, Szatmari P, Boyle M, 2013; Sanislow CA, Pine DS, Quinn KJ, et al, 2013). This is the nucleus of RDoC aims because children and adolescents with ADHD can be characterized in terms of several features that are best represented as dimensions and have well-theorized relationships to biological systems (Cuthbert \& Insel, 2013).

Recently evidence suggests that measures of child temperament may predict ADHD symptoms (Einziger et al., 2018). Temperament is a characteristic of personality (Buss \& Plomin, 1984; Crowell, 2016) and refers to individual, neurobiologically-based difference in reactivity, self-regulation and cognition (Eisenberg, 2012). It has been previously emphasized (Nigg J., 2016), that Hypotalamic-Pituitary-Adrenal (HPA) axis, through the cortisol hormone, may represent a powerful biological measure of behavioural self-regulatory systems, activity level, cognition, temperament (Stadler et al, 2011; Martel et al., 2009; Sonuga-Barke, 2005) and arousal (Snoek, Van Goozen, Matthys, Buitelaar, \& Engeland, 2004). Cortisol is released from the surrenal gland by means of the HPA axis activation, in response to catecholaminergic neurotransmitters (Ulrich-Lai \& Herman, 2009). Cortisol is involved in the regulation of a wide range of body functions, including emotion processing (Skosnik, Chatterton, Swisher, \& Park, 2000), awakening (Fries, Dettenborn, \& Kirschbaum, 2009) and stress responses (Chrousos, Kino, \& Charmandari, 2009). Both cortisol and temperament may share self-response regulatory processes (Martel et al., 2008; Nigg, 2016; Ulrich-Lai \& Herman, 2009), and one study on 70 healthy pre-schoolers indicates that children with SE temperament has higher morning salivary cortisol levels during their first week of a new primary school year (Davis, Donzella, Krueger, \& Gunnar, 1999), hypothesized as a stress-induced effect. To date, no studies have been conducted to study heterogeneity starting from the self-response regulatory processes between temperament and cortisol in children and adolescents with ADHD. As for clinical application of HPA-axis and cortisol level in ADHD diagnosis and dimension, available studies are, as yet, either inconsistent (Bonvicini, Faraone, \& Scassellati, 2016; Freitag et al, 2009, Corominas et al, 2012) or suggestive, but not significant, upon dimensional stratification of ADHD symptoms (Pinto et al., 2016). The aims of this study to contribute to the issue of clinical heterogeneity of ADHD, analysing whether ADHD symptoms and co-morbidity traits simultaneously link to both cortisol level and temperament dimensions, as biomarkers of arousal and inhibited behaviour. To pursue our aim we formulated five specific research questions: i) Do temperament dimensions and awakening cortisol level differ between children and adolescents with ADHD and TDC? ii) Do temperament dimensions and awakening cortisol levels correlate with dimension of ADHD core symptoms? iii) Does awakening cortisol level associate with any of the three-temperament dimension? iv) Do parent ratings of the oppositional and defiant traits and anxiety traits affect the association between temperament dimensions and cortisol levels with ADHD core symptoms in the ADHD group?

Interventions

Swanson, Noolan and Phelham - IV edition (SNAP-IV); Conners' Parent Rating Scales (CPRS)DIAGNOSTIC_TEST

* Ratings on the Swanson, Nolan and Pelham Evaluation Scale - IV (Bussing et al., 2008), were assessed during baseline visit for participants at the time of research assessment, to exclude the presence of ADHD symptoms in the healthy subjects. This scale is composed of 26 items for ADHD symptoms and ODD and was administered at baseline and at follow-up visit. * Temperament assessment: we used the Mary Rothbart's Temperament Questionnaire, a caregivers' report measure designed to provide a detailed assessment of temperament. * ADHD Rating scales: the Long Version of Conners' Parent Rating Scale (Conners et al., 1998) was used to quantify ADHD comorbidity symptoms, as ODD and Anxiety traits, in the children and adolescents with ADHD. * Salivary cortisol: Sampling was performed during one ordinary weekday between 7 and 8 o'clock, within 60' after nocturnal awakening.

Eligibility

Sex: ALLMin age: 3 YearsMax age: 16 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. ADHD group: * The assessment was completed as part of their routine psychiatric assessment using unstructured interview, screening of ADHD and other psychiatric symptoms through parent questionnaires, and direct observation with the participants, which led to a DSM-5-based diagnosis of ADHD; * Signed informed consent from parents or legal guardian and/or assent for youth aged \>12 y/o. 2. TDY (Typically Developing Control) - group: * Signed informed consent from parents or legal guardian and/or assent for youth aged \>12 y/o; * TDY were recruited from pre-school, primary and secondary schools in the local catchment area. * Assessment of the TDY was carried out by a clinician in schools through an unstructured interview with the parents and teachers. Exclusion Criteria: 1. ADHD group: * Not signed informed consent from parents or legal guardian and/or assent for youth aged \>12 y/o; * IQ below 70; * neurological and other psychiatric disorders; * genetic and/or medical conditions mimicking ADHD symptoms; * treatment with psychotropic medications other than ADHD medications; * TDY were also excluded if they presented with any learning or behavioural difficulties as reported in the parent and teacher interviews, as well as mild, moderate or severe symptoms of ADHD in the clinician-led rating scale. 2. TDY (Typically Developing Control) - group: * Not signed informed consent from parents or legal guardian and/or assent for youth aged \>12 y/o; * IQ below 70; * neurological and other psychiatric disorders; * genetic and/or medical conditions mimicking ADHD symptoms; * treatment with psychotropic medications other than ADHD medications.

Outcomes

Primary Outcomes

To examine the association of ADHD with temperament dimensions and low cortisol levels, building on previous research that these may represent potential markers of low behaviour inhibition and under-arousal in the disorder.

Specifically: * we first investigate whether temperament dimensions and awakening cortisol level differ between youths with ADHD and controls and correlate with ADHD symptoms (inattention and hyperactivity-impulsivity). * Second, we examine whether the three temperament dimensions are associated with awakening cortisol levels.

Time frame: six months

To evaluate the association between cortisol levels and co-morbidity severity symptoms.

We test the association of oppositional-defiant and anxiety traits with the temperament dimensions and cortisol levels, and whether the association of ADHD with each temperament or cortisol measure remains when controlling for these comorbid psychiatric traits.