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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
153
single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only
single-dose placebo capsule during the fMRI session only
McLean Hospital
Belmont, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dopamine Active Transporter Binding Potential
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
Time frame: 1 hour PET scan (Session 3)
The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress
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.
Time frame: 3 hour EEG Session (Session 4)
The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress
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.
Time frame: 3 hour EEG Session (Session 4)
Cortisol Output in Response to a Stress Manipulation
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.
Time frame: 3 hour EEG Session (Session 4)
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues
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.
Time frame: 3 hour Drug & fMRI Session (Session 2)
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback
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.
Time frame: 3 hour Session 2 (fMRI session)
The Effect of Diagnosis on Cortisol Reactivity
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.
Time frame: 3 hour EEG Session (Session 4)
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