Brain Inflammation Study

Summary of Study:

Major depressive disorder (MDD) may manifest via chronic neuroinflammation. The translocator protein (TSPO), located on the outer mitochondrial membrane of microglia and astrocytes, is regarded as a marker of this neuroinflammation and can be measured by positron emission tomography (PET). 

In humans, anti-inflammatory medications such as celecoxib can be used. Celecoxib has antidepressant effects in MDD; however, the observed effect sizes are highly variable, likely reflecting the biological heterogeneity of MDD. We hypothesize that anti-inflammatory treatments such as celecoxib will be most effective in those with the neuroinflammatory subtype of MDD (high brain inflammation) and that the mechanism of antidepressant action is through a reduction of neuroinflammation. 

We will test these hypotheses in humans by recruiting 42 participants and treating them with celecoxib (8 weeks, 400mg/day).  Participants will receive TSPO PET imaging (to quantify brain inflammation) before and after treatment. 

Brain Imaging 

This study involved brain imaging with Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI).  

These imaging modalities allow us to gain a lot of information about the brain, including:

• PET: We can assess inflammation in every region of the brain.  A review of PET imaging of brain inflammation in psychiatric disorders can be found here.  Note, we use the PET tracer called FEPPA in this study.

• structural MRI: Tells you the size and shape of every brain region.  See an example here.  (Different colors represent different brain regions.)  We have automated techniques (e.g., Freesurfer) to extract volume/thickness of each region. 

The PET brain imaging is performed both before and after treatment. 

Participant Questionnaires

Our participants completed the following surveys prior to treatment:

Adult Rejection Sensitivity Questionnaire (taken before and after treatment)

Childhood Trauma Questionnaire

Credibility And Expectancy Questionnaire 

Edinburgh Handedness Inventory

Hamilton Depression Rating Scale (taken before, during and after treatment)

Highly Sensitive Person Scale (taken before and after treatment)

Hurt Feelings Questionnaire (taken before and after treatment)

Inventory Of Depression And Anxiety (taken before and after treatment)

Multidimensional Scale Of Perceived Social Support

Quick Inventory Of Depressive Symptoms (taken before and after treatment)

Revised Social Anhedonia Scale (taken before and after treatment)

Sleep Questionnaire (taken before and after treatment)

Social Responsiveness Scale (taken before and after treatment)

Insomnia Severity Index (taken before and after treatment)

Because there may be a gut-brain link involving inflammation:

IBS - Symptom Severity Scale (taken before and after treatment)

IBS- Quality of Life (taken before and after treatment)

NIH Promis  (taken before and after treatment)

The following topics are currently being prepared for manuscripts by our students and interns:

• John Fitzgerald (Stony Brook University): Examination of whether high pretreatment brain inflammation (assessed by PET) is associated with response to treatment with the anti-inflammatory, celecoxib.  Examination of whether change in brain inflammation is associated with the change in depression.  (joined lab January 2023)

• Samantha Goldstein (Stony Brook University): Relationship between early life stress, social support and brain inflammation (joined lab as an intern in September 2017)