<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/NCT01701258</url>
  </required_header>
  <id_info>
    <org_study_id>2012P002593</org_study_id>
    <secondary_id>5R01MH095809</secondary_id>
    <nct_id>NCT01701258</nct_id>
  </id_info>
  <brief_title>An Investigation of Early Life Stress and Depression</brief_title>
  <official_title>Early Life Stress and Depression: Molecular and Functional Imaging Approaches</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mclean Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mclean Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate brain pathways within adult females (with a&#xD;
      history of CSA that occurred between the ages of 5-14) with and without a current diagnosis&#xD;
      of major depressive disorder (MDD).&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      The CSA/MDD participants will be characterized by (1) reduced reward responsiveness and&#xD;
      prefrontal cortex activity, but increased cortisol levels, (2) reduced dopamine activity, and&#xD;
      (3) reduced dopamine transporter binding. The over-arching purpose of the study is to (1)&#xD;
      identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent&#xD;
      re-victimization, and (3) develop more targeted therapeutic interventions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will include four sessions:&#xD;
&#xD;
      Session 1 (SCID Session) The first session takes place at the Center for Depression, Anxiety,&#xD;
      and Stress Research (CDASR) or Neuroimaging Center (both at McLean Hospital) and involves&#xD;
      consenting, a clinical evaluation, a series of questionnaires, and a medical assessment.&#xD;
&#xD;
      Session 2 or 3 (fMRI Session) The third session takes place at the Neuroimaging Center. Using&#xD;
      a double-blind design, participants will be administered either amisulpride (50 mg) or&#xD;
      placebo. Participants will complete the Monetary Incentive Delay (MID) task during functional&#xD;
      magnetic resonance imaging (fMRI) and the Probabilistic Stimulus Selection Task (PSST)&#xD;
      afterwards.&#xD;
&#xD;
      Session 2 or 3 (PET Session) This session takes place at Massachusetts General Hospital. 9&#xD;
      mCi of [11C] altropane will be injected by a trained nuclear medicine technician and positron&#xD;
      emission tomography (PET) scanning will begin. Prior to the PET scan, a blood serum pregnancy&#xD;
      test will be administered for females.&#xD;
&#xD;
      Session 4 (ERP Session) The fourth session takes place at the CDASR and involves an&#xD;
      electroencephalography (EEG) recording, the Probabilistic Reward Task (PRT), and collecting&#xD;
      saliva samples to assess cortisol levels.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2013</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>There were four groups of subjects: those with a history of child sexual abuse that are currently experiencing a major depressive episode, those with a history of child sexual abuse without a current or past diagnosis of major depressive disorder, those without a history of child sexual abuse that are currently experiencing a major depressive episode, and those with without a history of child sexual abuse and without a current or past diagnosis of major depressive disorder. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo for the fMRI session (session 2 or 3).</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dopamine Active Transporter Binding Potential</measure>
    <time_frame>1 hour PET scan (Session 3)</time_frame>
    <description>Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential.&#xD;
Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue.&#xD;
*Higher BPND scores indicate greater binding potential</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress</measure>
    <time_frame>3 hour EEG Session (Session 4)</time_frame>
    <description>The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress</measure>
    <time_frame>3 hour EEG Session (Session 4)</time_frame>
    <description>EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress.&#xD;
Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cortisol Output in Response to a Stress Manipulation</measure>
    <time_frame>3 hour EEG Session (Session 4)</time_frame>
    <description>This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues</measure>
    <time_frame>3 hour Drug &amp; fMRI Session (Session 2)</time_frame>
    <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback</measure>
    <time_frame>3 hour Session 2 (fMRI session)</time_frame>
    <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effect of Diagnosis on Cortisol Reactivity</measure>
    <time_frame>3 hour EEG Session (Session 4)</time_frame>
    <description>This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve.&#xD;
Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.</description>
  </primary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Major Depressive Disorder (MDD)</condition>
  <condition>History of Childhood Sexual Abuse (CSA)</condition>
  <arm_group>
    <arm_group_label>CSA/MDD-amisulpride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CSA/MDD-placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CSA/RES-amisulpride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CSA/RES-placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MDD-amisulpride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MDD-placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control-amisulpride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control-placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amisulpride</intervention_name>
    <description>single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
    <arm_group_label>CSA/MDD-amisulpride</arm_group_label>
    <arm_group_label>CSA/RES-amisulpride</arm_group_label>
    <arm_group_label>Control-amisulpride</arm_group_label>
    <arm_group_label>MDD-amisulpride</arm_group_label>
    <other_name>Solian</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>single-dose placebo capsule during the fMRI session only</description>
    <arm_group_label>CSA/MDD-placebo</arm_group_label>
    <arm_group_label>CSA/RES-placebo</arm_group_label>
    <arm_group_label>Control-placebo</arm_group_label>
    <arm_group_label>MDD-placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          -  Females of all ethnic origins, age between 20 and 45; right-handed (Chapman &amp; Chapman&#xD;
             1987);&#xD;
&#xD;
          -  Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine;&#xD;
             6 months for neuroleptics; 2 weeks for benzodiazepines; 2 weeks for any other&#xD;
             antidepressants);&#xD;
&#xD;
        Inclusion Criteria for Childhood Sexual Abuse/MDD (CSA/MDD) Group:&#xD;
&#xD;
          -  At least one incident of contact sexual abuse1 between the ages 5-14 years;&#xD;
&#xD;
          -  Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of the SCID);&#xD;
&#xD;
        Inclusion Criteria for Childhood Sexual Abuse/Resilient (CSA/RES) Group:&#xD;
&#xD;
          -  At least one incident of contact sexual abuse1 between the ages 5-14 years;&#xD;
&#xD;
          -  Absence of past or current DSM diagnosis, including MDD or alcohol/substance abuse;&#xD;
&#xD;
        Inclusion Criteria for Non-traumatized, MDD (MDD) Group:&#xD;
&#xD;
          -  No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic&#xD;
             Antecedents Questionnaire);&#xD;
&#xD;
          -  Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of SCID);&#xD;
&#xD;
        Non-traumatized, healthy controls (controls):&#xD;
&#xD;
          -  No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic&#xD;
             Antecedents Questionnaire);&#xD;
&#xD;
          -  Absence of any medical, neurological, and psychiatric illness (including&#xD;
             alcohol/substance abuse)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with suicidal ideation where study participation is deemed unsafe by the&#xD;
             study clinician;&#xD;
&#xD;
          -  Pregnant women or women of childbearing potential who are not compliant with the&#xD;
             requirements of a urine and blood pregnancy test.&#xD;
&#xD;
          -  Failure to meet MRI or PET safety requirements.&#xD;
&#xD;
          -  Serious or unstable medical illness, including cardiovascular, hepatic, renal,&#xD;
             respiratory, endocrine (hypothyroidism), neurologic or hematologic disease;&#xD;
&#xD;
          -  Past/current DSM diagnosis of: OCD, ADHD, schizophrenia, schizoaffective disorder,&#xD;
             delusional disorder, bipolar disorder, mood congruent/incongruent psychotic features,&#xD;
             substance dependence, substance abuse within the last 12 months (with the exception of&#xD;
             cocaine or stimulant abuse, which will lead to automatic exclusion);&#xD;
&#xD;
          -  Simple phobia, social anxiety disorder and generalized anxiety disorders will be&#xD;
             allowed only if secondary to MDD and only in the CSA/MDD and MDD groups (which will be&#xD;
             matched for comorbidities);&#xD;
&#xD;
          -  History of seizure disorder; renal insufficiency; history of adverse reactions to&#xD;
             amisulpride;&#xD;
&#xD;
          -  History of cocaine, stimulant, and other DA drug use [e.g., (meth)amphetamine),&#xD;
             methylphenidate].&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diego Pizzagalli, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mclean Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McLean Hospital</name>
      <address>
        <city>Belmont</city>
        <state>Massachusetts</state>
        <zip>02478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Kaiser RH, Clegg R, Goer F, Pechtel P, Beltzer M, Vitaliano G, Olson DP, Teicher MH, Pizzagalli DA. Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response. Psychol Med. 2018 May;48(7):1157-1166. doi: 10.1017/S0033291717002628. Epub 2017 Sep 25.</citation>
    <PMID>28942738</PMID>
  </results_reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <results_first_submitted>March 21, 2018</results_first_submitted>
  <results_first_submitted_qc>May 16, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">May 18, 2018</results_first_posted>
  <last_update_submitted>May 16, 2018</last_update_submitted>
  <last_update_submitted_qc>May 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mclean Hospital</investigator_affiliation>
    <investigator_full_name>Diego A. Pizzagalli</investigator_full_name>
    <investigator_title>Associate Professor of Psychiatry, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>Depression</keyword>
  <keyword>Childhood Sexual Abuse</keyword>
  <keyword>Dopamine</keyword>
  <keyword>MRI</keyword>
  <keyword>PET</keyword>
  <keyword>ERP</keyword>
  <keyword>Stress</keyword>
  <keyword>Reward</keyword>
  <keyword>Childhood trauma</keyword>
  <keyword>Amisulpride</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Stress, Psychological</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amisulpride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT01701258/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited at McLean Hospital (Belmont, MA) between August, 2013, and June, 2017. The study was advertised using flyers, and on a number of internet bulletin boards available to the general public. Study visits were conducted in research facilities at McLean Hospital and Massachusetts General Hospital.</recruitment_details>
      <pre_assignment_details>In session 1, subjects had a diagnostic interview, a physical exam, provided a blood sample, and completed surveys, to determine eligibility. Those eligible were invited to participate in the other sessions. Participants did not need to complete all sessions. The order depended on facility availability and convenience for participants.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants</title>
          <description>All participants that went through the assessment (session 1) regardless if they were eligible or ineligible.</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
        </group>
        <group group_id="P3">
          <title>Control-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible control subjects without a history of child sexual abuse and without a current or past diagnosis of major depression were invited to participate in the fMRI session. Those that were interested were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible baseline control participants did not complete this session.</description>
        </group>
        <group group_id="P4">
          <title>Control-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible control subjects without a history of child sexual abuse and without a current or past diagnosis of major depression were invited to participate in the fMRI session. Those that were interested were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible baseline control participants did not complete this session.</description>
        </group>
        <group group_id="P5">
          <title>MDD Group</title>
          <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode .</description>
        </group>
        <group group_id="P6">
          <title>MDD-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects without a history of child sexual abuse that are currently experiencing a major depressive episode were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="P7">
          <title>MDD-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects without a history of child sexual abuse that are currently experiencing a major depressive episode were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="P8">
          <title>CSA/RES</title>
          <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
        </group>
        <group group_id="P9">
          <title>CSA/RES-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.This arm is specific to those that competed the fMRI session. Many eligible CSA/RES baseline participants did not complete this session.</description>
        </group>
        <group group_id="P10">
          <title>CSA/RES-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible CSA/RES baseline participants did not complete this session.</description>
        </group>
        <group group_id="P11">
          <title>CSA/MDD Group</title>
          <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA).</description>
        </group>
        <group group_id="P12">
          <title>CSA/MDD-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a current episode of major depression (MDD) with a history of child sexual abuse (CSA) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.This arm is specific to those that competed the fMRI session. Many eligible CSA/MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="P13">
          <title>CSA/MDD-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a current episode of major depression (MDD) with a history of child sexual abuse (CSA) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo. This arm is specific to those that competed the fMRI session.&#xD;
Many eligible CSA/MDD baseline participants did not complete this session.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Assessment and Scheduling</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="153"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible After Screening Visit</title>
              <participants_list>
                <participants group_id="P1" count="96"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Returned for Drug+fMRI (Session 2)</title>
              <participants_list>
                <participants group_id="P1" count="68"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Returned for PET (Session 3)</title>
              <participants_list>
                <participants group_id="P1" count="73"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Returned for EEG (Session 4)</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="83"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Found to be Ineligible</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator Terminated</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Drug+fMRI (Session 2)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="8"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="6"/>
                <participants group_id="P10" count="6"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="10"/>
                <participants group_id="P13" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Drug Challenge</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="8"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="6"/>
                <participants group_id="P10" count="6"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="10"/>
                <participants group_id="P13" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="8"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="6"/>
                <participants group_id="P10" count="6"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="10"/>
                <participants group_id="P13" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>PET (Session 3)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="16"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="19"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="18"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="16"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="19"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="18"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>EEG (Session 4)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="16"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="17"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="16"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="17"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
                <participants group_id="P10" count="0"/>
                <participants group_id="P11" count="0"/>
                <participants group_id="P12" count="0"/>
                <participants group_id="P13" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Our baseline population are the 96 individuals that were eligible for the study after the screening visit. Not all participants that were eligible after the screening visit went on to participate in the other study sessions. Baseline data were collected for all eligible participants in each cohort during the assessment and scheduling period.</population>
      <group_list>
        <group group_id="B1">
          <title>Control Group</title>
          <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
        </group>
        <group group_id="B2">
          <title>MDD Group</title>
          <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
        </group>
        <group group_id="B3">
          <title>CSA/RES Group</title>
          <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
        </group>
        <group group_id="B4">
          <title>CSA/MDD Group</title>
          <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="24"/>
            <count group_id="B4" value="29"/>
            <count group_id="B5" value="96"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="29"/>
                    <measurement group_id="B5" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.44" spread="6.64"/>
                    <measurement group_id="B2" value="27.19" spread="5.99"/>
                    <measurement group_id="B3" value="25.61" spread="4.94"/>
                    <measurement group_id="B4" value="29.95" spread="6.91"/>
                    <measurement group_id="B5" value="26.63" spread="6.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="29"/>
                    <measurement group_id="B5" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="29"/>
                    <measurement group_id="B5" value="96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BDI II</title>
          <description>Measure Description: Beck Depression Inventory-II (BDI-II). Measures the presence and severity of 21 depressive symptoms during the past two weeks, on a scale from 0 (none, or no change) to 3 (persistent, or worsening).Range: 0 to 63. Higher scores indicate greater symptom severity. Clinical categories for total score: 0-14: absent; 14-19: mild; 20-28: moderate; 29-63: severe.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.68" spread="2.79"/>
                    <measurement group_id="B2" value="27.23" spread="8.44"/>
                    <measurement group_id="B3" value="3.83" spread="5.77"/>
                    <measurement group_id="B4" value="31.49" spread="9.05"/>
                    <measurement group_id="B5" value="15.95" spread="15.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MASQ total</title>
          <description>Measure Description: Mood and Anxiety Symptom Questionnaire (MASQ), short form. Measures the severity of anxiety and depressive symptoms.62 items, rating of how much you have experienced certain feelings, emotions, or behaviors in the past week; item responses are on a 5-point scale from 1 (not at all) to 5 (extremely).&#xD;
Range: 62-310; higher scores indicates more severe symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93.04" spread="16.27"/>
                    <measurement group_id="B2" value="167.86" spread="22.60"/>
                    <measurement group_id="B3" value="101.82" spread="26.19"/>
                    <measurement group_id="B4" value="180.57" spread="21.89"/>
                    <measurement group_id="B5" value="135.42" spread="44.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Dopamine Active Transporter Binding Potential</title>
        <description>Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential.&#xD;
Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue.&#xD;
*Higher BPND scores indicate greater binding potential</description>
        <time_frame>1 hour PET scan (Session 3)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Group</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
          </group>
          <group group_id="O2">
            <title>MDD Group</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES Group</title>
            <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
          </group>
          <group group_id="O4">
            <title>CSA/MDD Group</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
        </group_list>
        <measure>
          <title>Dopamine Active Transporter Binding Potential</title>
          <description>Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential.&#xD;
Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue.&#xD;
*Higher BPND scores indicate greater binding potential</description>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="19"/>
                <count group_id="O4" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Caudate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.191" spread="0.124"/>
                    <measurement group_id="O2" value="3.161" spread="0.139"/>
                    <measurement group_id="O3" value="3.175" spread="0.130"/>
                    <measurement group_id="O4" value="3.216" spread="0.136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Putamen</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.361" spread="0.120"/>
                    <measurement group_id="O2" value="3.359" spread="0.134"/>
                    <measurement group_id="O3" value="3.241" spread="0.125"/>
                    <measurement group_id="O4" value="3.318" spread="0.131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accumbens</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.159" spread="0.109"/>
                    <measurement group_id="O2" value="2.103" spread="0.122"/>
                    <measurement group_id="O3" value="2.103" spread="0.122"/>
                    <measurement group_id="O4" value="2.149" spread="0.119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress</title>
        <description>The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.</description>
        <time_frame>3 hour EEG Session (Session 4)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Group</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
          </group>
          <group group_id="O2">
            <title>MDD Group</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES Group</title>
            <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
          </group>
          <group group_id="O4">
            <title>CSA/MDD Group</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress</title>
          <description>The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.</description>
          <units>Ratio (Response Bias Score)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PRT Block1: Before MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.028" spread="0.035"/>
                    <measurement group_id="O2" value="0.117" spread="0.045"/>
                    <measurement group_id="O3" value="0.092" spread="0.043"/>
                    <measurement group_id="O4" value="0.167" spread="0.070"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PRT Block2: Before MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.124" spread="0.046"/>
                    <measurement group_id="O2" value="0.155" spread="0.048"/>
                    <measurement group_id="O3" value="0.130" spread="0.082"/>
                    <measurement group_id="O4" value="0.168" spread="0.102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PRT Block1: After MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.128" spread="0.026"/>
                    <measurement group_id="O2" value="0.078" spread="0.055"/>
                    <measurement group_id="O3" value="0.079" spread="0.042"/>
                    <measurement group_id="O4" value="0.048" spread="0.042"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PRT Block2: After MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.245" spread="0.041"/>
                    <measurement group_id="O2" value="0.128" spread="0.035"/>
                    <measurement group_id="O3" value="0.143" spread="0.052"/>
                    <measurement group_id="O4" value="0.127" spread="0.050"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress</title>
        <description>EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress.&#xD;
Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.</description>
        <time_frame>3 hour EEG Session (Session 4)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Group</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
          </group>
          <group group_id="O2">
            <title>MDD Group</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES Group</title>
            <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
          </group>
          <group group_id="O4">
            <title>CSA/MDD Group</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress</title>
          <description>EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress.&#xD;
Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.</description>
          <units>amplitude (microvolts)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.71" spread="0.86"/>
                    <measurement group_id="O2" value="4.75" spread="1.15"/>
                    <measurement group_id="O3" value="2.16" spread="0.92"/>
                    <measurement group_id="O4" value="4.15" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post MAST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.06" spread="0.91"/>
                    <measurement group_id="O2" value="4.99" spread="1.22"/>
                    <measurement group_id="O3" value="2.30" spread="0.98"/>
                    <measurement group_id="O4" value="3.90" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cortisol Output in Response to a Stress Manipulation</title>
        <description>This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.</description>
        <time_frame>3 hour EEG Session (Session 4)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Group</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
          </group>
          <group group_id="O2">
            <title>MDD Group</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES Group</title>
            <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
          </group>
          <group group_id="O4">
            <title>CSA/MDD Group</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
        </group_list>
        <measure>
          <title>Cortisol Output in Response to a Stress Manipulation</title>
          <description>This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.</description>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cort1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.80" spread="1.27"/>
                    <measurement group_id="O2" value="12.53" spread="2.11"/>
                    <measurement group_id="O3" value="10.15" spread="2.27"/>
                    <measurement group_id="O4" value="14.19" spread="1.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cort2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.11" spread="2.44"/>
                    <measurement group_id="O2" value="12.28" spread="1.70"/>
                    <measurement group_id="O3" value="9.51" spread="1.89"/>
                    <measurement group_id="O4" value="8.63" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cort3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.55" spread="4.91"/>
                    <measurement group_id="O2" value="15.23" spread="1.65"/>
                    <measurement group_id="O3" value="10.75" spread="2.19"/>
                    <measurement group_id="O4" value="14.31" spread="2.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cort4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.89" spread="4.07"/>
                    <measurement group_id="O2" value="16.30" spread="3.24"/>
                    <measurement group_id="O3" value="8.99" spread="1.75"/>
                    <measurement group_id="O4" value="14.22" spread="2.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cort5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.07" spread="1.80"/>
                    <measurement group_id="O2" value="10.34" spread="1.15"/>
                    <measurement group_id="O3" value="7.41" spread="1.36"/>
                    <measurement group_id="O4" value="11.01" spread="2.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues</title>
        <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
        <time_frame>3 hour Drug &amp; fMRI Session (Session 2)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CSA/MDD-amisulpride</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O2">
            <title>CSA/MDD-placebo</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES-amisulpride</title>
            <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O4">
            <title>CSA/RES-placebo</title>
            <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O5">
            <title>MDD-amisulpride</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O6">
            <title>MDD-placebo</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O7">
            <title>Control-amisulpride</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O8">
            <title>Control-placebo</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
        </group_list>
        <measure>
          <title>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues</title>
          <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
          <units>beta weight (slope)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="11"/>
                <count group_id="O8" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Caudate Response to Reward Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".514" spread=".199"/>
                    <measurement group_id="O2" value=".054" spread=".238"/>
                    <measurement group_id="O3" value=".511" spread=".257"/>
                    <measurement group_id="O4" value=".079" spread=".257"/>
                    <measurement group_id="O5" value=".403" spread=".209"/>
                    <measurement group_id="O6" value=".608" spread=".222"/>
                    <measurement group_id="O7" value=".200" spread=".189"/>
                    <measurement group_id="O8" value=".468" spread=".189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Caudate Response to Neutral Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".254" spread=".161"/>
                    <measurement group_id="O2" value="-.243" spread=".192"/>
                    <measurement group_id="O3" value=".050" spread=".208"/>
                    <measurement group_id="O4" value="-.370" spread=".208"/>
                    <measurement group_id="O5" value=".047" spread=".170"/>
                    <measurement group_id="O6" value=".156" spread=".180"/>
                    <measurement group_id="O7" value=".222" spread=".154"/>
                    <measurement group_id="O8" value=".185" spread=".154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Putamen Response to Reward Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".550" spread=".175"/>
                    <measurement group_id="O2" value=".468" spread=".209"/>
                    <measurement group_id="O3" value=".745" spread=".226"/>
                    <measurement group_id="O4" value=".419" spread=".226"/>
                    <measurement group_id="O5" value=".698" spread=".185"/>
                    <measurement group_id="O6" value=".814" spread=".196"/>
                    <measurement group_id="O7" value=".608" spread=".162"/>
                    <measurement group_id="O8" value=".663" spread=".167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Putamen Response to Neutral Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".550" spread=".175"/>
                    <measurement group_id="O2" value=".357" spread=".168"/>
                    <measurement group_id="O3" value=".493" spread=".181"/>
                    <measurement group_id="O4" value=".240" spread=".181"/>
                    <measurement group_id="O5" value=".384" spread=".148"/>
                    <measurement group_id="O6" value=".621" spread=".157"/>
                    <measurement group_id="O7" value=".455" spread=".134"/>
                    <measurement group_id="O8" value=".518" spread=".134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accumbens Response to Reward Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".692" spread=".206"/>
                    <measurement group_id="O2" value=".255" spread=".247"/>
                    <measurement group_id="O3" value=".679" spread=".267"/>
                    <measurement group_id="O4" value=".310" spread=".267"/>
                    <measurement group_id="O5" value=".351" spread=".218"/>
                    <measurement group_id="O6" value=".428" spread=".231"/>
                    <measurement group_id="O7" value=".401" spread=".197"/>
                    <measurement group_id="O8" value=".480" spread=".197"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accumbens Response to Neutral Cues</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".385" spread=".173"/>
                    <measurement group_id="O2" value=".040" spread=".207"/>
                    <measurement group_id="O3" value="-.123" spread=".224"/>
                    <measurement group_id="O4" value="-.381" spread=".224"/>
                    <measurement group_id="O5" value="-.111" spread=".183"/>
                    <measurement group_id="O6" value=".140" spread=".194"/>
                    <measurement group_id="O7" value=".016" spread=".165"/>
                    <measurement group_id="O8" value=".120" spread=".165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback</title>
        <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
        <time_frame>3 hour Session 2 (fMRI session)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CSA/MDD-amisulpride</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O2">
            <title>CSA/MDD-placebo</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES-amisulpride</title>
            <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O4">
            <title>CSA/RES-placebo</title>
            <description>Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O5">
            <title>MDD-amisulpride</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O6">
            <title>MDD-placebo</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
          <group group_id="O7">
            <title>Control-amisulpride</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.&#xD;
Amisulpride: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only</description>
          </group>
          <group group_id="O8">
            <title>Control-placebo</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session.&#xD;
Placebo: single-dose placebo capsule during the fMRI session only</description>
          </group>
        </group_list>
        <measure>
          <title>Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback</title>
          <description>This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID).&#xD;
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.</description>
          <units>beta weight (slope)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="8"/>
                <count group_id="O7" value="11"/>
                <count group_id="O8" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Caudate Response to Reward Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.101" spread=".329"/>
                    <measurement group_id="O2" value=".040" spread=".393"/>
                    <measurement group_id="O3" value="-.197" spread=".425"/>
                    <measurement group_id="O4" value="-.905" spread=".425"/>
                    <measurement group_id="O5" value="-.819" spread=".347"/>
                    <measurement group_id="O6" value="-.773" spread=".368"/>
                    <measurement group_id="O7" value="-.613" spread=".314"/>
                    <measurement group_id="O8" value="-.273" spread=".314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Caudate Response to Neutral Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.233" spread=".314"/>
                    <measurement group_id="O2" value="-.608" spread=".376"/>
                    <measurement group_id="O3" value="-.501" spread=".406"/>
                    <measurement group_id="O4" value="-.959" spread=".406"/>
                    <measurement group_id="O5" value="-.865" spread=".331"/>
                    <measurement group_id="O6" value="-.733" spread=".352"/>
                    <measurement group_id="O7" value="-.793" spread=".300"/>
                    <measurement group_id="O8" value="-.105" spread=".300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Putamen Response to Reward Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.018" spread=".217"/>
                    <measurement group_id="O2" value=".063" spread=".260"/>
                    <measurement group_id="O3" value="-.087" spread=".281"/>
                    <measurement group_id="O4" value="-.304" spread=".281"/>
                    <measurement group_id="O5" value="-.031" spread=".229"/>
                    <measurement group_id="O6" value="-.357" spread=".243"/>
                    <measurement group_id="O7" value="-.533" spread=".207"/>
                    <measurement group_id="O8" value="-.131" spread=".207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Putamen Response to Neutral Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.021" spread=".201"/>
                    <measurement group_id="O2" value="-.418" spread=".240"/>
                    <measurement group_id="O3" value="-.142" spread=".260"/>
                    <measurement group_id="O4" value="-.276" spread=".260"/>
                    <measurement group_id="O5" value="-.229" spread=".221"/>
                    <measurement group_id="O6" value="-.108" spread=".225"/>
                    <measurement group_id="O7" value="-.375" spread=".192"/>
                    <measurement group_id="O8" value=".164" spread=".192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accumbens Response to Reward Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.158" spread=".421"/>
                    <measurement group_id="O2" value=".839" spread=".503"/>
                    <measurement group_id="O3" value="-.046" spread=".544"/>
                    <measurement group_id="O4" value="-.713" spread=".544"/>
                    <measurement group_id="O5" value="-.554" spread=".444"/>
                    <measurement group_id="O6" value="-.215" spread=".471"/>
                    <measurement group_id="O7" value=".074" spread=".401"/>
                    <measurement group_id="O8" value=".069" spread=".401"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accumbens Response to Neutral Feedback</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".010" spread=".308"/>
                    <measurement group_id="O2" value="-.332" spread=".368"/>
                    <measurement group_id="O3" value="-.079" spread=".398"/>
                    <measurement group_id="O4" value="-.819" spread=".398"/>
                    <measurement group_id="O5" value="-.456" spread=".325"/>
                    <measurement group_id="O6" value="-.039" spread=".345"/>
                    <measurement group_id="O7" value="-.503" spread=".294"/>
                    <measurement group_id="O8" value=".109" spread=".294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Effect of Diagnosis on Cortisol Reactivity</title>
        <description>This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve.&#xD;
Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.</description>
        <time_frame>3 hour EEG Session (Session 4)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Control Group</title>
            <description>Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode.</description>
          </group>
          <group group_id="O2">
            <title>MDD Group</title>
            <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
          <group group_id="O3">
            <title>CSA/RES Group</title>
            <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES).</description>
          </group>
          <group group_id="O4">
            <title>CSA/MDD Group</title>
            <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge.</description>
          </group>
        </group_list>
        <measure>
          <title>The Effect of Diagnosis on Cortisol Reactivity</title>
          <description>This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve.&#xD;
Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.</description>
          <units>[log (ng/ml)]*min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="156.58" spread="10.72"/>
                    <measurement group_id="O2" value="186.78" spread="12.20"/>
                    <measurement group_id="O3" value="152.13" spread="12.20"/>
                    <measurement group_id="O4" value="179.16" spread="11.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 years, 10 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>All Participants</title>
          <description>All participants that went through the assessment (session 1) regardless if they were eligible or ineligible.</description>
        </group>
        <group group_id="E2">
          <title>All Baseline Participants</title>
          <description>Participants that were eligible for the study after the screening visit (session 1). These participants were invited to participate in the other study sessions.</description>
        </group>
        <group group_id="E3">
          <title>Control Group</title>
          <description>Control subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode. These participants were eligible after the screening session (session 1) and are accounted for regardless if they completed other study sessions.</description>
        </group>
        <group group_id="E4">
          <title>Control-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible control subjects without a history of child sexual abuse and without a current or past diagnosis of major depression were invited to participate in the fMRI session. Those that were interested, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible baseline control participants did not complete this session.</description>
        </group>
        <group group_id="E5">
          <title>Control-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible control subjects without a history of child sexual abuse and without a current or past diagnosis of major depression were invited to participate in the fMRI session. Those that were interested, were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible baseline control participants did not complete this session.</description>
        </group>
        <group group_id="E6">
          <title>MDD Group</title>
          <description>Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode. These participants were eligible after the screening session (session 1) and are accounted for regardless if they completed other study sessions.</description>
        </group>
        <group group_id="E7">
          <title>MDD-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects without a history of child sexual abuse that are currently experiencing a major depressive episode were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="E8">
          <title>MDD-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects without a history of child sexual abuse that are currently experiencing a major depressive episode were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="E9">
          <title>CSA/RES</title>
          <description>Subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES). These participants were eligible after the screening session (session 1) and are accounted for regardless if they completed other study sessions.</description>
        </group>
        <group group_id="E10">
          <title>CSA/RES-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.This arm is specific to those that competed the fMRI session. Many eligible CSA/RES baseline participants did not complete this session.</description>
        </group>
        <group group_id="E11">
          <title>CSA/RES-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a history of CSA but no psychopathology (&quot;resilient group&quot;; CSA/RES) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo during the fMRI session. This arm is specific to those that competed the fMRI session. Many eligible CSA/RES baseline participants did not complete this session.</description>
        </group>
        <group group_id="E12">
          <title>CSA/MDD Group</title>
          <description>Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA). These participants were eligible after the screening session (session 1) and are accounted for regardless if they completed other study sessions.</description>
        </group>
        <group group_id="E13">
          <title>CSA/MDD-amisulpride (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a current episode of major depression (MDD) with a history of child sexual abuse (CSA) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.This arm is specific to those that competed the fMRI session. Many eligible CSA/MDD baseline participants did not complete this session.</description>
        </group>
        <group group_id="E14">
          <title>CSA/MDD-placebo (fMRI Session)</title>
          <description>After the screening visit, eligible subjects with a current episode of major depression (MDD) with a history of child sexual abuse (CSA) were invited to participate in the fMRI session. Those that were interested in participating, were randomized to receive a placebo. This arm is specific to those that competed the fMRI session.&#xD;
Many eligible CSA/MDD baseline participants did not complete this session.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Other Adverse Events</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="153"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E11" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E12" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E13" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E14" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The choice of a 50-mg dose of amisulpride was based on animal work showing low doses potentiate striatal dopamine release, have strong hedonic effects, and increase the incentive value of environmental cues. Higher doses may have different results.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Diego Pizzagalli, Ph.D.</name_or_title>
      <organization>McLean Hospital</organization>
      <phone>617-855-4230</phone>
      <email>dap@mclean.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01701258
org study id: 2012P002593
secondary id: 5R01MH095809
nct id: NCT01701258
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to investigate brain pathways within adult females (with a
      history of CSA that occurred between the ages of 5-14) with and without a current diagnosis
      of major depressive disorder (MDD).

      Hypotheses:

      The CSA/MDD participants will be characterized by (1) reduced reward responsiveness and
      prefrontal cortex activity, but increased cortisol levels, (2) reduced dopamine activity, and
      (3) reduced dopamine transporter binding. The over-arching purpose of the study is to (1)
      identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent
      re-victimization, and (3) develop more targeted therapeutic interventions.
This study will include four sessions:

      Session 1 (SCID Session) The first session takes place at the Center for Depression, Anxiety,
      and Stress Research (CDASR) or Neuroimaging Center (both at McLean Hospital) and involves
      consenting, a clinical evaluation, a series of questionnaires, and a medical assessment.

      Session 2 or 3 (fMRI Session) The third session takes place at the Neuroimaging Center. Using
      a double-blind design, participants will be administered either amisulpride (50 mg) or
      placebo. Participants will complete the Monetary Incentive Delay (MID) task during functional
      magnetic resonance imaging (fMRI) and the Probabilistic Stimulus Selection Task (PSST)
      afterwards.

      Session 2 or 3 (PET Session) This session takes place at Massachusetts General Hospital. 9
      mCi of [11C] altropane will be injected by a trained nuclear medicine technician and positron
      emission tomography (PET) scanning will begin. Prior to the PET scan, a blood serum pregnancy
      test will be administered for females.

      Session 4 (ERP Session) The fourth session takes place at the CDASR and involves an
      electroencephalography (EEG) recording, the Probabilistic Reward Task (PRT), and collecting
      saliva samples to assess cortisol levels.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: There were four groups of subjects: those with a history of child sexual abuse that are currently experiencing a major depressive episode, those with a history of child sexual abuse without a current or past diagnosis of major depressive disorder, those without a history of child sexual abuse that are currently experiencing a major depressive episode, and those with without a history of child sexual abuse and without a current or past diagnosis of major depressive disorder. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo for the fMRI session (session 2 or 3).
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Dopamine Active Transporter Binding Potential
time frame: 1 hour PET scan (Session 3)
description: Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential.
Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue.
*Higher BPND scores indicate greater binding potential
measure: The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress
time frame: 3 hour EEG Session (Session 4)
description: The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.
measure: The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress
time frame: 3 hour EEG Session (Session 4)
description: EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress.
Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.
measure: Cortisol Output in Response to a Stress Manipulation
time frame: 3 hour EEG Session (Session 4)
description: This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.
measure: Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues
time frame: 3 hour Drug & fMRI Session (Session 2)
description: This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID).
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
measure: Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback
time frame: 3 hour Session 2 (fMRI session)
description: This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID).
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
measure: The Effect of Diagnosis on Cortisol Reactivity
time frame: 3 hour EEG Session (Session 4)
description: This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve.
Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.
arm group label: CSA/MDD-amisulpride
arm group type: Active Comparator
description: Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
arm group label: CSA/MDD-placebo
arm group type: Placebo Comparator
description: Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session.
arm group label: CSA/RES-amisulpride
arm group type: Active Comparator
description: Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
arm group label: CSA/RES-placebo
arm group type: Placebo Comparator
description: Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session.
arm group label: MDD-amisulpride
arm group type: Active Comparator
description: Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
arm group label: MDD-placebo
arm group type: Placebo Comparator
description: Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session.
arm group label: Control-amisulpride
arm group type: Active Comparator
description: Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
arm group label: Control-placebo
arm group type: Placebo Comparator
description: Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session.
intervention type: Drug
intervention name: Amisulpride
description: single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only
arm group label: CSA/MDD-amisulpride
arm group label: CSA/RES-amisulpride
arm group label: Control-amisulpride
arm group label: MDD-amisulpride
other name: Solian
intervention type: Drug
intervention name: Placebo
description: single-dose placebo capsule during the fMRI session only
arm group label: CSA/MDD-placebo
arm group label: CSA/RES-placebo
arm group label: Control-placebo
arm group label: MDD-placebo
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Diego Pizzagalli, PhD
role: Principal Investigator
affiliation: Mclean Hospital
facility: 
facility: 
country: United States
citation: Kaiser RH, Clegg R, Goer F, Pechtel P, Beltzer M, Vitaliano G, Olson DP, Teicher MH, Pizzagalli DA. Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response. Psychol Med. 2018 May;48(7):1157-1166. doi: 10.1017/S0033291717002628. Epub 2017 Sep 25.
PMID: 28942738
responsible party type: Principal Investigator
investigator affiliation: Mclean Hospital
investigator full name: Diego A. Pizzagalli
investigator title: Associate Professor of Psychiatry, Harvard Medical School
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Stress, Psychological
mesh term: Amisulpride
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The choice of a 50-mg dose of amisulpride was based on animal work showing low doses potentiate striatal dopamine release, have strong hedonic effects, and increase the incentive value of environmental cues. Higher doses may have different results.
point of contact: 