Identifying Correlates of Brain Microglial Activation in Neuropsychiatric Syndromes: A Dimensional Approach

  • STATUS
    Recruiting
  • End date
    Aug 22, 2021
  • participants needed
    200
  • sponsor
    The University of Texas Health Science Center, Houston
Updated on 22 January 2021

Summary

The purpose of this research is to determine whether there is more extensive inflammation in the brain of people with clinical evidence of neuropsychiatric syndromes, such as mood disorder, chronic pain syndrome, dementia, traumatic brain injury, or substance abuse. The research will also explore whether there is more inflammation in patients with more neuropsychiatric symptoms. Inflammation in the brain will identified by using Positron Emission Tomography (PET) with the radiotracer [11C]PBR-28.

Description

This study will explore whether brain microglial activation (which leads to an inflammatory response) is more extensive in individuals with clinical evidence of neuropsychiatric syndromes and whether the extent of microglial activation is proportional to the extent of neuropsychiatric symptoms.

More specifically, the hypothesis is that:

  1. Brain microglial activation is more substantial in the presence of neuropsychiatric illness, and the extent of brain microglial activation is proportional to severity of phenotypic presentation of neuropsychiatric illness (i.e. depression, cognitive impairment, fatigue, etc.) in a given patient.
  2. Specific brain regions where enhanced microglial activation is present underlie a portion of phenotypic variance in neuropsychiatric patients
  3. Combinations of neuropsychiatric phenotypes rather than specific differences in immune mechanisms underlie the contribution of central immune activation to a specific neuropsychiatric diagnosis.

The following measures will be obtained:

  1. microglial activation as quantified by PET using the radiotracer [11C]PBR-28. ([11C]PBR-28 specifically binds translocator protein (TSPO), which is associated with microglial activation and can thus serve as an in vivo biomarker of microglial activation and neuroinflammation. TSPO is also called the peripheral benzodiazepine receptor (PBR))
  2. dimension of specific neuropsychiatric symptoms (Hamilton Depression Rating Scale (HDRS), Montreal Cognitive Assessment (MoCA), Positive and Negative Affect Schedule (PANAS))
  3. presence/absence of a specific neuropsychiatric diagnosis (Dementing Illnesses, Traumatic Brain Injury, Major Depression, Bipolar Disorder, Pain Syndromes, Other Affective Disorders, etc.)

Using the above measures, correlations (and brain regional correlations) between the extent of microglial activation and the presence of a dimension of neuropsychiatric symptoms will be tested for. Following this, the presence of microglial activation (and brain regional microglial activation) 1) between healthy control volunteers and volunteers with neuropsychiatric syndromes and 2) between the various neuropsychiatric syndromes/diagnoses will be tested for.

Details
Condition Neuropsychiatric Syndromes
Treatment PET with radiotracer [11C]PBR-28, Affective challenge
Clinical Study IdentifierNCT03705715
SponsorThe University of Texas Health Science Center, Houston
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 45 yrs?
Gender: Male or Female
Do you have Neuropsychiatric Syndromes?
Do you have any of these conditions: Do you have Neuropsychiatric Syndromes??
Must be between 18-45 years old
Males or females
Must be right handed
Must be able to sit unaccompanied for long periods of time with little body movement
Must be illicit drug free at time of scanning as appropriate (UDS negative)
Must be either healthy (without medical, neurological, psychiatric illness) or have a diagnosis of a neuropsychiatric syndrome (mood disorder, chronic pain syndrome, dementias, traumatic brain injury, substance/alcohol use disorder)
Healthy Control volunteers must be medication free ( 14 days)
Illicit drug free at time of scanning (verified by negative urine drug screen)

Exclusion Criteria

Must not be a smoker
Females must not be pregnant or nursing
Must not suffer from claustrophobia
Must not meet exclusion criteria for MRI scanning (i.e. non-fixed magnetisable objects)
Must not be PBR-28 low or moderate affinity binder
Healthy control volunteers must not have on-going, chronic, or relapsing/remitting medical, psychiatric (absence of both DSM-IV Axis I and/or Axis II disorders), or neurological illness as determined by combination of history, medical record, and/or examination
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