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

Overview

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 or \[11C\]ER176.

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 or \[11C\]ER176. (\[11C\]PBR-28 and \[11C\]ER176 specifically bind 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.