<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03788902</url>
  </required_header>
  <id_info>
    <org_study_id>0017-13-SHA</org_study_id>
    <nct_id>NCT03788902</nct_id>
  </id_info>
  <brief_title>OT and Social Cognition in Children With ADHD: Impact of MPH</brief_title>
  <official_title>Oxytocin and Social Cognition in Children With Attention Deficit Hyperactivity Disorder: Impact of Methylphenidate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shalvata Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shalvata Mental Health Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: The current study aimed to explore the possible effect of stimulants on oxytocin&#xD;
      (OT), a neuropeptide found to regulate social behavior, as a mediator of the pro-social&#xD;
      effect of methylphenidate (MPH) in children with attention deficit hyperactivity disorder&#xD;
      (ADHD) compared to healthy controls (HCs). Methods: In a double-blind manner the&#xD;
      investigators compared the performance of 50 children with ADHD and 40 HCs in &quot;theory of&#xD;
      mind&quot; (ToM) tasks and examined the effect of a single dose of MPH/placebo on ToM and salivary&#xD;
      OT levels in children with ADHD at baseline and following an interpersonal interaction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder affecting&#xD;
      approximately 7% of children and adolescents, is associated with considerable impairments in&#xD;
      social functioning. Children with ADHD, in comparison to healthy children, suffer from more&#xD;
      social rejection and problems in reciprocal relationships. Deficits in interpersonal&#xD;
      functioning in children with ADHD have been attributed in previous studies to, among other&#xD;
      things, impairments in theory of mind (ToM) - the ability to attribute mental states,&#xD;
      beliefs, and intentions to self and to others. For example, some studies have shown deficits&#xD;
      in the ability to recognize facial expressions among children with ADHD. Other studies have&#xD;
      found impairments in first- and second-order ToM tests. There is also evidence showing that&#xD;
      empathic functions in children with ADHD are impaired. However, small sample sizes, as well&#xD;
      as high percentages of comorbid disruptive disorders, served as limitations in these studies.&#xD;
&#xD;
      One's ToM ability depends on, among other things, the integrity of dopaminergic and&#xD;
      serotonergic systems, as well as on their interaction with other neurotransmitters and&#xD;
      neurohormones (e.g., acetylcholine, oxytocin).&#xD;
&#xD;
      Oxytocin (OT) is a neuropeptide found to accelerate the formation of social relationships,&#xD;
      the expression of behaviors of closeness, and the recognition of affect in the facial&#xD;
      expressions of others. Oxytocin has been hypothesized to raise the salience of social cues by&#xD;
      modulating attention-orienting responses to external contextual social cues. Its secretion&#xD;
      increases in response to interpersonal interactions. Studies found connections between blood&#xD;
      and saliva OT levels, OT receptor gene polymorphism, and the strength of social relationships&#xD;
      and behaviors in healthy individuals, as well as in patients suffering from mental disorders.&#xD;
      Oxytocin reciprocally interacts with dopaminergic neurons in the mesolimbic tract. Anatomical&#xD;
      and immonucytochemical studies have found that neuronal fibers and receptor binding-sites of&#xD;
      OT and dopamine are located in the same areas in the central nervous system (CNS), sometimes&#xD;
      in very close proximity to one another. Oxytocin-secreting cells in the hypothalamus carry&#xD;
      dopamine receptors. Indeed, patients with mental disorders related to dysregulation of&#xD;
      dopamine (e.g., autistic spectrum disorders, schizophrenia, depression) show changes in their&#xD;
      CNS and peripheral OT levels. Given the fact that injury of dopaminergic transporters and&#xD;
      receptors is a central component in the etiology of ADHD, it is also possible that OT plays a&#xD;
      role as a mediator of social deficits, and mainly in ToM impairment in children with ADHD.&#xD;
&#xD;
      To date, only a few studies have shown decreased OT levels in children with ADHD when&#xD;
      compared to healthy controls. These studies found a negative correlation between serum OT&#xD;
      levels and ADHD rating scale total scores, and aggression scores, and a positive correlation&#xD;
      between the serum OT level and empathy scores in patients with ADHD. However, in both&#xD;
      studies, only baseline OT levels were assessed; therefore, changes in OT levels following an&#xD;
      interpersonal interaction were not measured. This is an important point, as social abilities&#xD;
      are dynamic and interaction-related; the reactivity of the OT system to interpersonal&#xD;
      interaction is thus probably highly relevant to the understanding of social difficulties in&#xD;
      ADHD patients.&#xD;
&#xD;
      Stimulants reduce negative social interactions and improve social and behavioral functioning&#xD;
      in children with ADHD, and also improve empathy scores. In a previous study, the&#xD;
      investigators showed that a single dose of methylphenidate (MPH) improved the performance of&#xD;
      children with ADHD on ToM tests. To date, no study examined a possible effect of stimulants&#xD;
      on OT levels in children with ADHD. This is a pivotal issue in the understanding of the&#xD;
      neurobiological underpinnings of improvement in social cognition measures among children with&#xD;
      ADHD who are treated with stimulants, given that OT might have a role in mediating this&#xD;
      improvement.&#xD;
&#xD;
      In the current study the investigators hypothesized that dysfunction in the OT system may&#xD;
      account for the social difficulties of children suffering from ADHD and that the dynamics in&#xD;
      the OT system may explain the pro-social effect of stimulants on these children. Thus, the&#xD;
      objectives of the current study were 1) to compare ToM measures and salivary OT levels&#xD;
      between children with ADHD and healthy controls (HCs), and 2) to examine the effect of a&#xD;
      single dose of MPH on ToM and salivary OT levels in children with ADHD following an&#xD;
      interpersonal interaction.&#xD;
&#xD;
      Methods Subjects Fifty children aged 6-12 diagnosed with ADHD and 40 HCs were recruited.&#xD;
      Patients were recruited from the ADHD clinic and the outpatient clinic of the Shalvata Mental&#xD;
      Health Center, School of Medicine, Tel-Aviv University. The HCs subjects were recruited from&#xD;
      the community via the internet and social media.&#xD;
&#xD;
      ADHD was diagnosed by child and adolescent psychiatrists using the Diagnostic and Statistical&#xD;
      Manual of Mental Disorders, fourth or fifth edition (DSM-IV-TR and DSM-5). The investigators&#xD;
      excluded children with a past or current affective disorder, psychosis, substance abuse,&#xD;
      conduct disorder or any medical or neurological condition or medication-taking that might&#xD;
      affect the child's participation in the study. The investigators also excluded children who&#xD;
      had a first-degree relative with a major psychiatric diagnosis.&#xD;
&#xD;
      Inclusion criteria for the control group were the same as those of the ADHD group but with no&#xD;
      diagnosis of ADHD or a first-degree relative with ADHD.&#xD;
&#xD;
      Participants were reimbursed for their expanses in participation and received a small present&#xD;
      as appreciation. The IRB approved the study. Both parents of all participants signed a&#xD;
      consent form and the children gave their consent verbally.&#xD;
&#xD;
      Procedure Apart from the initial clinical assessment at the clinic, all assessments were&#xD;
      performed in the children's homes. Children with ADHD participated in two sessions: one&#xD;
      session an hour after taking a short-acting MPH (in an adjusted dosage of 0.3-0.5mg/kg) and&#xD;
      one session an hour after taking a placebo (PLC). Children routinely prescribed with MPH&#xD;
      treatment were asked not to take the medicine 48 hours before the examination, since the&#xD;
      clinical effect of the long-acting MPH is no longer than 12 hours. The study was&#xD;
      randomized-controlled, such that children were assigned to the sessions randomly in a&#xD;
      double-blind manner. Each session lasted about 60-90 minutes. In order to lessen a possible&#xD;
      learning effect of the computerized tasks (to be elaborated upon forthwith), the sessions&#xD;
      were performed at least two weeks apart. Control subjects participated in only one session&#xD;
      and did not take any medication.&#xD;
&#xD;
      Parents completed questionnaires regarding demographics and general information about the&#xD;
      child's academic and social functioning. In addition, parents completed the Swanson, Nolan&#xD;
      and Pelham Questionnaire-IV (SNAP-IV). This instrument contains subscales for inattention,&#xD;
      hyperactive/impulsive behavior, and oppositional behavior.&#xD;
&#xD;
      Parents also filled out the Strengths and Difficulties Questionnaire (SDQ), a screening&#xD;
      inventory composed of five distinct dimensions: conduct problems, emotional symptoms,&#xD;
      hyperactivity, peer problems, and pro-social behavior. Intelligence was measured using the&#xD;
      similarities subtest from the Wechsler Intelligence Scale for Children version IV (WISC-IV).&#xD;
      Self-reported anxiety was measured using the State-Trait Anxiety Inventory (STAI), a 40-item&#xD;
      questionnaire scored by a Likert scale. State anxiety represents a transient emotional status&#xD;
      that results from situational stress; trait anxiety represents a predisposition to react with&#xD;
      anxiety in stressful situations.&#xD;
&#xD;
      The investigators measured ToM performance using the ToM test, which test consists of&#xD;
      vignettes, stories, and drawings about which the child has to answer a number of questions.&#xD;
      Results are given on three subscales: ToM1 - precursors of ToM (i.e., recognition of&#xD;
      emotions); ToM2 - first manifestations of a real ToM (first-order belief, understanding of&#xD;
      false belief); and ToM3 - more advanced aspects of ToM (second-order belief, understanding of&#xD;
      humor). The second ToM task was the Faux Pas Recognition task (FPR), designed by Baron-Cohen&#xD;
      et al.. This task is designated to evaluate the ability of participants to recognize social&#xD;
      &quot;faux pas&quot; - social situations in which a speaker says something without understanding that&#xD;
      there might be a difference between his/her state of knowledge and that of the listener&#xD;
      (&quot;cognitive&quot; ToM), and should recognize the potential emotional impact of a statement on the&#xD;
      listener (&quot;affective&quot; ToM). At each session, participants were given 10 short stories, five&#xD;
      of which contained faux pas situations to be identified. After hearing every story,&#xD;
      participants were asked ToM questions. The score consisted of the total number of all correct&#xD;
      identifications of a faux pas situation. The Hebrew version of the FPR was employed after&#xD;
      validation by a group of normative subjects.&#xD;
&#xD;
      Executive functions and attention were tested via the cognition module in the NIH Toolbox for&#xD;
      the Assessment of Neurological and Behavioral Function (NIH-TB). The investigators used the&#xD;
      Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control and Attention&#xD;
      Test, which measure cognitive flexibility and inhibitory control, respectively.&#xD;
&#xD;
      Salivary OT levels were measured at three time points: at the beginning of each session&#xD;
      (&quot;T1&quot;), 40 minutes after the administration of MPH/PLC (&quot;T2&quot;; only for the ADHD group), and&#xD;
      15 minutes after a &quot;positive social interaction&quot; in which the child and the parent were asked&#xD;
      to plan a &quot;fun day&quot; that would include both of them, and to talk about it for five minutes&#xD;
      (&quot;T3&quot;). Participants were asked to avoid drinking and eating an hour before the test and to&#xD;
      avoid caffeine three hours before the test.&#xD;
&#xD;
      Saliva samples were collected by passive drool. In order to precipitate the mucus, samples&#xD;
      underwent three freeze-thaw cycles: freeze at -70°C and thaw at 4°C. After the forth cycle&#xD;
      the tubes were centrifuged twice at 1500 x g (4000 rpm) for 30 minutes. Supernatants were&#xD;
      collected and stored at -20°C until assayed. Determination of OT from saliva samples was&#xD;
      performed using a commercial OT ELISA kit (ENZO, NY, USA). Measurements were performed in&#xD;
      duplicate according to the manufacturer's instructions. The concentrations of samples were&#xD;
      calculated using MatLab-7 according to relevant standard curves. The intra-assay and&#xD;
      inter-assay coefficients of samples were 14.7 and 22.7 percent, respectively. The intra-assay&#xD;
      and inter-assay coefficients of controls were 4.9 and 13.2 percent, respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2014</start_date>
  <completion_date type="Actual">January 1, 2017</completion_date>
  <primary_completion_date type="Actual">December 1, 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes in scores of ToM test</measure>
    <time_frame>20 minutes</time_frame>
    <description>ToM test - consists of vignettes, stories, and drawings about which the child has to answer a number of questions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in scores of Faux-Pas Recognition test</measure>
    <time_frame>15 minutes</time_frame>
    <description>number of faux-pas recognized in specific vignettes by participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in Oxytocin salivary level</measure>
    <time_frame>2 hours</time_frame>
    <description>Oxytocin salivary levels as measured three/two times during the examination (ADHD group and healthy control accordingly).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>ADHD group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group was examined twice - once after taking Ritalin and once after taking placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Children with the same demographics as children with ADHD but without ADHD or a first degree relative with ADHD</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritalin</intervention_name>
    <description>Single dose of Ritalin IR 0.3-0.5 mg/kg OR placebo</description>
    <arm_group_label>ADHD group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 6-12 years&#xD;
&#xD;
          -  Diagnosis of ADHD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past or current affective disorder, psychosis, substance abuse, conduct disorder&#xD;
&#xD;
          -  Any medical or neurological condition or medication-taking that might affect the&#xD;
             child's participation in the study&#xD;
&#xD;
          -  First-degree relative with a major psychiatric diagnosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hagai Maoz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shalvata Mental Health Center</affiliation>
  </overall_official>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>December 26, 2018</last_update_submitted>
  <last_update_submitted_qc>December 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shalvata Mental Health Center</investigator_affiliation>
    <investigator_full_name>Yuval Bloch</investigator_full_name>
    <investigator_title>Head of child and adolescent outpatient clinic</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkinesis</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03788902
org study id: 0017-13-SHA
nct id: NCT03788902
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Background: The current study aimed to explore the possible effect of stimulants on oxytocin
      (OT), a neuropeptide found to regulate social behavior, as a mediator of the pro-social
      effect of methylphenidate (MPH) in children with attention deficit hyperactivity disorder
      (ADHD) compared to healthy controls (HCs). Methods: In a double-blind manner the
      investigators compared the performance of 50 children with ADHD and 40 HCs in "theory of
      mind" (ToM) tasks and examined the effect of a single dose of MPH/placebo on ToM and salivary
      OT levels in children with ADHD at baseline and following an interpersonal interaction.
Attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder affecting
      approximately 7% of children and adolescents, is associated with considerable impairments in
      social functioning. Children with ADHD, in comparison to healthy children, suffer from more
      social rejection and problems in reciprocal relationships. Deficits in interpersonal
      functioning in children with ADHD have been attributed in previous studies to, among other
      things, impairments in theory of mind (ToM) - the ability to attribute mental states,
      beliefs, and intentions to self and to others. For example, some studies have shown deficits
      in the ability to recognize facial expressions among children with ADHD. Other studies have
      found impairments in first- and second-order ToM tests. There is also evidence showing that
      empathic functions in children with ADHD are impaired. However, small sample sizes, as well
      as high percentages of comorbid disruptive disorders, served as limitations in these studies.

      One's ToM ability depends on, among other things, the integrity of dopaminergic and
      serotonergic systems, as well as on their interaction with other neurotransmitters and
      neurohormones (e.g., acetylcholine, oxytocin).

      Oxytocin (OT) is a neuropeptide found to accelerate the formation of social relationships,
      the expression of behaviors of closeness, and the recognition of affect in the facial
      expressions of others. Oxytocin has been hypothesized to raise the salience of social cues by
      modulating attention-orienting responses to external contextual social cues. Its secretion
      increases in response to interpersonal interactions. Studies found connections between blood
      and saliva OT levels, OT receptor gene polymorphism, and the strength of social relationships
      and behaviors in healthy individuals, as well as in patients suffering from mental disorders.
      Oxytocin reciprocally interacts with dopaminergic neurons in the mesolimbic tract. Anatomical
      and immonucytochemical studies have found that neuronal fibers and receptor binding-sites of
      OT and dopamine are located in the same areas in the central nervous system (CNS), sometimes
      in very close proximity to one another. Oxytocin-secreting cells in the hypothalamus carry
      dopamine receptors. Indeed, patients with mental disorders related to dysregulation of
      dopamine (e.g., autistic spectrum disorders, schizophrenia, depression) show changes in their
      CNS and peripheral OT levels. Given the fact that injury of dopaminergic transporters and
      receptors is a central component in the etiology of ADHD, it is also possible that OT plays a
      role as a mediator of social deficits, and mainly in ToM impairment in children with ADHD.

      To date, only a few studies have shown decreased OT levels in children with ADHD when
      compared to healthy controls. These studies found a negative correlation between serum OT
      levels and ADHD rating scale total scores, and aggression scores, and a positive correlation
      between the serum OT level and empathy scores in patients with ADHD. However, in both
      studies, only baseline OT levels were assessed; therefore, changes in OT levels following an
      interpersonal interaction were not measured. This is an important point, as social abilities
      are dynamic and interaction-related; the reactivity of the OT system to interpersonal
      interaction is thus probably highly relevant to the understanding of social difficulties in
      ADHD patients.

      Stimulants reduce negative social interactions and improve social and behavioral functioning
      in children with ADHD, and also improve empathy scores. In a previous study, the
      investigators showed that a single dose of methylphenidate (MPH) improved the performance of
      children with ADHD on ToM tests. To date, no study examined a possible effect of stimulants
      on OT levels in children with ADHD. This is a pivotal issue in the understanding of the
      neurobiological underpinnings of improvement in social cognition measures among children with
      ADHD who are treated with stimulants, given that OT might have a role in mediating this
      improvement.

      In the current study the investigators hypothesized that dysfunction in the OT system may
      account for the social difficulties of children suffering from ADHD and that the dynamics in
      the OT system may explain the pro-social effect of stimulants on these children. Thus, the
      objectives of the current study were 1) to compare ToM measures and salivary OT levels
      between children with ADHD and healthy controls (HCs), and 2) to examine the effect of a
      single dose of MPH on ToM and salivary OT levels in children with ADHD following an
      interpersonal interaction.

      Methods Subjects Fifty children aged 6-12 diagnosed with ADHD and 40 HCs were recruited.
      Patients were recruited from the ADHD clinic and the outpatient clinic of the Shalvata Mental
      Health Center, School of Medicine, Tel-Aviv University. The HCs subjects were recruited from
      the community via the internet and social media.

      ADHD was diagnosed by child and adolescent psychiatrists using the Diagnostic and Statistical
      Manual of Mental Disorders, fourth or fifth edition (DSM-IV-TR and DSM-5). The investigators
      excluded children with a past or current affective disorder, psychosis, substance abuse,
      conduct disorder or any medical or neurological condition or medication-taking that might
      affect the child's participation in the study. The investigators also excluded children who
      had a first-degree relative with a major psychiatric diagnosis.

      Inclusion criteria for the control group were the same as those of the ADHD group but with no
      diagnosis of ADHD or a first-degree relative with ADHD.

      Participants were reimbursed for their expanses in participation and received a small present
      as appreciation. The IRB approved the study. Both parents of all participants signed a
      consent form and the children gave their consent verbally.

      Procedure Apart from the initial clinical assessment at the clinic, all assessments were
      performed in the children's homes. Children with ADHD participated in two sessions: one
      session an hour after taking a short-acting MPH (in an adjusted dosage of 0.3-0.5mg/kg) and
      one session an hour after taking a placebo (PLC). Children routinely prescribed with MPH
      treatment were asked not to take the medicine 48 hours before the examination, since the
      clinical effect of the long-acting MPH is no longer than 12 hours. The study was
      randomized-controlled, such that children were assigned to the sessions randomly in a
      double-blind manner. Each session lasted about 60-90 minutes. In order to lessen a possible
      learning effect of the computerized tasks (to be elaborated upon forthwith), the sessions
      were performed at least two weeks apart. Control subjects participated in only one session
      and did not take any medication.

      Parents completed questionnaires regarding demographics and general information about the
      child's academic and social functioning. In addition, parents completed the Swanson, Nolan
      and Pelham Questionnaire-IV (SNAP-IV). This instrument contains subscales for inattention,
      hyperactive/impulsive behavior, and oppositional behavior.

      Parents also filled out the Strengths and Difficulties Questionnaire (SDQ), a screening
      inventory composed of five distinct dimensions: conduct problems, emotional symptoms,
      hyperactivity, peer problems, and pro-social behavior. Intelligence was measured using the
      similarities subtest from the Wechsler Intelligence Scale for Children version IV (WISC-IV).
      Self-reported anxiety was measured using the State-Trait Anxiety Inventory (STAI), a 40-item
      questionnaire scored by a Likert scale. State anxiety represents a transient emotional status
      that results from situational stress; trait anxiety represents a predisposition to react with
      anxiety in stressful situations.

      The investigators measured ToM performance using the ToM test, which test consists of
      vignettes, stories, and drawings about which the child has to answer a number of questions.
      Results are given on three subscales: ToM1 - precursors of ToM (i.e., recognition of
      emotions); ToM2 - first manifestations of a real ToM (first-order belief, understanding of
      false belief); and ToM3 - more advanced aspects of ToM (second-order belief, understanding of
      humor). The second ToM task was the Faux Pas Recognition task (FPR), designed by Baron-Cohen
      et al.. This task is designated to evaluate the ability of participants to recognize social
      "faux pas" - social situations in which a speaker says something without understanding that
      there might be a difference between his/her state of knowledge and that of the listener
      ("cognitive" ToM), and should recognize the potential emotional impact of a statement on the
      listener ("affective" ToM). At each session, participants were given 10 short stories, five
      of which contained faux pas situations to be identified. After hearing every story,
      participants were asked ToM questions. The score consisted of the total number of all correct
      identifications of a faux pas situation. The Hebrew version of the FPR was employed after
      validation by a group of normative subjects.

      Executive functions and attention were tested via the cognition module in the NIH Toolbox for
      the Assessment of Neurological and Behavioral Function (NIH-TB). The investigators used the
      Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control and Attention
      Test, which measure cognitive flexibility and inhibitory control, respectively.

      Salivary OT levels were measured at three time points: at the beginning of each session
      ("T1"), 40 minutes after the administration of MPH/PLC ("T2"; only for the ADHD group), and
      15 minutes after a "positive social interaction" in which the child and the parent were asked
      to plan a "fun day" that would include both of them, and to talk about it for five minutes
      ("T3"). Participants were asked to avoid drinking and eating an hour before the test and to
      avoid caffeine three hours before the test.

      Saliva samples were collected by passive drool. In order to precipitate the mucus, samples
      underwent three freeze-thaw cycles: freeze at -70°C and thaw at 4°C. After the forth cycle
      the tubes were centrifuged twice at 1500 x g (4000 rpm) for 30 minutes. Supernatants were
      collected and stored at -20°C until assayed. Determination of OT from saliva samples was
      performed using a commercial OT ELISA kit (ENZO, NY, USA). Measurements were performed in
      duplicate according to the manufacturer's instructions. The concentrations of samples were
      calculated using MatLab-7 according to relevant standard curves. The intra-assay and
      inter-assay coefficients of samples were 14.7 and 22.7 percent, respectively. The intra-assay
      and inter-assay coefficients of controls were 4.9 and 13.2 percent, respectively.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: changes in scores of ToM test
time frame: 20 minutes
description: ToM test - consists of vignettes, stories, and drawings about which the child has to answer a number of questions.
measure: changes in scores of Faux-Pas Recognition test
time frame: 15 minutes
description: number of faux-pas recognized in specific vignettes by participants
measure: changes in Oxytocin salivary level
time frame: 2 hours
description: Oxytocin salivary levels as measured three/two times during the examination (ADHD group and healthy control accordingly).
arm group label: ADHD group
arm group type: Experimental
description: This group was examined twice - once after taking Ritalin and once after taking placebo
arm group label: Healthy control
arm group type: No Intervention
description: Children with the same demographics as children with ADHD but without ADHD or a first degree relative with ADHD
intervention type: Drug
intervention name: Ritalin
description: Single dose of Ritalin IR 0.3-0.5 mg/kg OR placebo
arm group label: ADHD group
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hagai Maoz, MD
role: Principal Investigator
affiliation: Shalvata Mental Health Center
responsible party type: Principal Investigator
investigator affiliation: Shalvata Mental Health Center
investigator full name: Yuval Bloch
investigator title: Head of child and adolescent outpatient clinic
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Methylphenidate
sharing ipd: No