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Completed

NCT Number: NCT01701258

An Investigation of Early Life Stress and Depression

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.

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Key information

Age range

20 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

McLean Hospital, Belmont, Massachusetts, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

General Inclusion Criteria:

  • Females of all ethnic origins, age between 20 and 45; right-handed (Chapman & Chapman 1987);
  • Absence of any psychotropic medications for at least 2 weeks (6 weeks for fluoxetine; 6 months for neuroleptics; 2 weeks for benzodiazepines; 2 weeks for any other antidepressants);

Inclusion criteria

for Childhood Sexual Abuse/MDD (CSA/MDD) Group:

  • At least one incident of contact sexual abuse1 between the ages 5-14 years;
  • Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of the SCID);

Inclusion criteria

for Childhood Sexual Abuse/Resilient (CSA/RES) Group:

  • At least one incident of contact sexual abuse1 between the ages 5-14 years;
  • Absence of past or current DSM diagnosis, including MDD or alcohol/substance abuse;

Inclusion criteria

for Non-traumatized, MDD (MDD) Group:

  • No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of SCID);

Non-traumatized, healthy controls (controls):

  • No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
  • Absence of any medical, neurological, and psychiatric illness (including alcohol/substance abuse)

Exclusion criteria

  • Participants with suicidal ideation where study participation is deemed unsafe by the study clinician;
  • Pregnant women or women of childbearing potential who are not compliant with the requirements of a urine and blood pregnancy test.
  • Failure to meet MRI or PET safety requirements.
  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine (hypothyroidism), neurologic or hematologic disease;
  • Past/current DSM diagnosis of: OCD, ADHD, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, mood congruent/incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion);
  • Simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD and only in the CSA/MDD and MDD groups (which will be matched for comorbidities);
  • History of seizure disorder; renal insufficiency; history of adverse reactions to amisulpride;
  • History of cocaine, stimulant, and other DA drug use [e.g., (meth)amphetamine), methylphenidate].

Treatment and study plan

Amisulpride

Drug

single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only

Other names: Solian

Placebo

Drug

single-dose placebo capsule during the fMRI session only

Primary outcomes

  1. Dopamine Active Transporter Binding Potential

    Time frame: 1 hour PET scan (Session 3)

    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

  2. The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress

    Time frame: 3 hour EEG Session (Session 4)

    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.

  3. 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)

    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.
  4. Cortisol Output in Response to a Stress Manipulation

    Time frame: 3 hour EEG Session (Session 4)

    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.

  5. 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)

    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.

  6. 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)

    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.

  7. The Effect of Diagnosis on Cortisol Reactivity

    Time frame: 3 hour EEG Session (Session 4)

    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.

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • Massachusetts General Hospital
  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Early Life Stress and Depression: Molecular and Functional Imaging Approaches

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Oct 5, 2012
Registry last updated
May 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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