Clinical trial NCT01701258: An Investigation of Early Life Stress and Depression
Official title: Early Life Stress and Depression: Molecular and Functional Imaging Approaches
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Depressive Disorder (MDD)
History of Childhood Sexual Abuse (CSA)
Keywords: Depression
Childhood Sexual Abuse
Dopamine
MRI
PET
ERP
Stress
Reward
Childhood trauma
Amisulpride
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Massachusetts General Hospital
First posted: 2012-10-05
Enrollment: 153
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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 \[e.g., (meth)amphetamine), methylphenidate\].

Primary outcomes:
measure: Dopamine Active Transporter Binding Potential
timeFrame: 1 hour PET scan (Session 3)
measure: The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress
timeFrame: 3 hour EEG Session (Session 4)
measure: The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress
timeFrame: 3 hour EEG Session (Session 4)
measure: Cortisol Output in Response to a Stress Manipulation
timeFrame: 3 hour EEG Session (Session 4)
measure: Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues
timeFrame: 3 hour Drug & fMRI Session (Session 2)
measure: Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback
timeFrame: 3 hour Session 2 (fMRI session)
measure: The Effect of Diagnosis on Cortisol Reactivity
timeFrame: 3 hour EEG Session (Session 4)
Secondary outcomes:
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Diego Pizzagalli, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: Liu Y, Admon R, Mellem MS, Belleau EL, Kaiser RH, Clegg R, Beltzer M, Goer F, Vitaliano G, Ahammad P, Pizzagalli DA. Machine Learning Identifies Large-Scale Reward-Related Activity Modulated by Dopaminergic Enhancement in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):163-172. doi: 10.1016/j.bpsc.2019.10.002. Epub 2019 Oct 22.