Using an Anticipatory Shock Stress-induction fMRI Task to Challenge Mood-Related Stress-Circuitry

607 

Abstract Submission 

Mark Kvarta¹, Akram Yusuf², Josh Chiappelli², L. Elliot Hong³, Carlos Zarate¹

¹National Institute of Mental Health/NIH, Bethesda, MD, ²University of Maryland Baltimore, Baltimore, MD, ³University of Texas Houston, Houston, TX

Mark Kvarta, MD, PhD  
National Institute of Mental Health/NIH
Bethesda, MD

Akram Yusuf, BS  
University of Maryland Baltimore
Baltimore, MD

Josh Chiappelli, BS  
University of Maryland Baltimore
Baltimore, MD

L. Elliot Hong, MD  
University of Texas Houston
Houston, TX

Carlos Zarate, MD  
National Institute of Mental Health/NIH
Bethesda, MD

How stress across the lifespan impacts brain circuitry to contribute to psychiatric symptoms remains unclear. Brain areas responsible for processing stress have been implicated in depression including limbic areas like the hippocampus and reward areas. Stress-based tasks may be key to understanding how past and current stress experience intersect with symptoms in relevant brain regions. We hypothesized lifetime stress-induced perturbation of stress-sensitive cortico-limbic brain areas leads to altered activation in response to subsequent stressful situations, underlying altered stress responsivity in major depressive disorder (MDD) and contributing to symptoms.

The ankle shock threat (AST) paradigm is analogous to classic behavioral stress tasks in animals using foot shock and unpredictability, while human fMRI compatible and ethical. For this pilot, we recruited 26 patients with MDD (19/26 female) and 30 psychiatrically healthy adult controls (HC, 17/30 female). Major life stress (Childhood Trauma Questionnaire-CTQ) and recent stress (past 30 days) was recorded (Perceived Stress Scale-PSS). State (current) and trait (longitudinal) depressive symptoms were measured (Maryland State and Trait Depression Scale). Imaging was completed using a 3-T Siemens Prisma scanner and 64-channel coil, with an electrode attached to one ankle of each participant. A pre-determined intensity of shock was applied for 0.1s intermittently during the task (similar to a static shock, Transcutaneous Aversive Stimulator, Coulborne Instruments). There were 3 conditions: (1) "shock" in which a several shocks are delivered while a color signal on screen indicate shocks are likely; (2) "threat" in which the same color is present but no shock is given; and (3) "safe" with safety signal present. All preprocessing included slice timing correction and volume co-registration. Images were linearly detrended, normalized into MNI standard space, and spatially smoothed (FWHM=8mm) using SPM12. First level models were developed for each subject with all volumes in a single analysis regressing the conditions. The contrast of interest was "threat"–"safe" to study threat processing but without the interference of actual shock. Regression analyses were completed in SPSS (IBM). All experimental protocols approved by the University of Maryland Baltimore IRB.

Nominally significant group differences were found in multiple regions from the threat-safe contrast (p<0.05) in previous analyses. Two regions with significant patient-control differences were selected for this pilot depression study due to roles in stress processing and symptomatology: right hippocampus and ventral anterior cingulate. In controls, state and trait depression scores were highly correlated with each other (r=+0.67, p<0.001), and both correlated with recent stress PSS (state r=0.62 p<0.001; trait r=0.46 p=0.015). In MDD, PSS was associated with only state (r=0.66, p<0.001), but not trait depression. CTQ predicted trait depression (r=0.59, p=0.02), but not state depression (p=0.5). In the AST, PSS correlated negatively with R Hippocampal activation (r=-0.45, p=0.026), while CTQ was negatively associated with vACC activation (r=-0.64, p=0.01). There were no significant stress-activation associations in controls, revealing a differential relationship in stress activation and regulation.

We observed relationships between current stress and depressive symptoms, but differing associations between historical stress and stress task-related brain activity in MDD. Activity in this task revealed lifetime stress impact on vACC, key to reward processing and implicated in anhedonia, and recent stress impact on hippocampus, key to stress regulation and linked to MDD symptoms. These findings support a mechanism of altered stress vulnerability and stress processing in MDD, and provide support for stress-based tasks in disorders in which stress processing is dysregulated.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Emotional Perception

Activation (eg. BOLD task-fMRI) ²

ADULTS

Affective Disorders

FUNCTIONAL MRI

Psychiatric Disorders