Obsessive-compulsive disorder: Puzzles and prospects

Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study.

Neuroinflammation in psychiatric disorders: PET imaging and promising new targets.

A growing need exists for reliable in-vivo measurement of neuroinflammation to better characterise the inflammatory processes underlying various diseases and to inform the development of novel therapeutics that target deleterious glial activity. PET is well suited to quantify neuroinflammation and has the potential to discriminate components of the neuroimmune response. However, there are several obstacles to the reliable quantification of neuroinflammation by PET imaging. Despite these challenges, PET studies have consistently identified associations between neuroimmune responses and pathophysiology in brain disorders such as Alzheimer's disease. Tissue studies have also begun to clarify the meaning of changes in PET signal in some diseases. Furthermore, although PET imaging of neuroinflammation does not have an established clinical application, novel targets are under investigation and a small but growing number of studies have suggested that this imaging modality could have a role in drug development. Future studies are needed to further improve our knowledge of the cellular mechanisms that underlie changes in PET signal, how immune response contributes to neurological disease, and how it might be therapeutically modified.

PET imaging of neuroinflammation in neurological disorders

http://diposit.ub.edu/dspace/bitstream/2445/171755/1/687088.pdf

Early intervention for obsessive compulsive disorder: An expert consensus statement

Importance For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO). Translocator protein density increases when microglia are activated during neuroinflammation and the TSPO distribution volume (V T ) is an index of TSPO density. Objective To determine whether TSPO V T is elevated in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex in OCD. Design, Setting, and Participants This case-control study was conducted at a tertiary care psychiatric hospital from May 1, 2010, to November 30, 2016. Participants with OCD (n = 20) and age-matched healthy control individuals (n = 20) underwent a fluorine F 18–labeled N -(2-(2-fluoroethoxy)benzyl)- N -(4-phenoxypyridin-3-yl)acetamide PET scan. It is a high-quality second-generation TSPO-binding PET radiotracer. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures The TSPO V T was measured in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex. Compulsions were assessed with the Yale-Brown Obsessive Compulsive Scale. Results In the OCD and healthy groups, the mean (SD) ages were 27.4 (7.1) years and 27.6 (6.6) years, respectively, and 11 (55%) and 8 (40%) were women, respectively. In OCD, TSPO V T was significantly elevated in these brain regions (mean, 32%; range, 31%-36% except anterior cingulate cortex, 24%; analysis of variance, effect of diagnosis: P P  = .004). Slightly lower elevations in TSPO V T (22%-29%) were present in other gray matter regions. The Yale-Brown Obsessive Compulsive Scale measure of distress associated with preventing compulsive behaviors significantly correlated with TSPO V T in the orbitofrontal cortex (uncorrected Pearson correlation r  = 0.62; P  = .005). Conclusions and Relevance To our knowledge, this is the first study demonstrating inflammation within the neurocircuitry of OCD. The regional distribution of elevated TSPO V T argues that the autoimmune/neuroinflammatory theories of OCD should extend beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit. Immunomodulatory therapies should be investigated in adult OCD, rather than solely childhood OCD, particularly in cases with prominent distress when preventing compulsions.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder.

Serotonin transporter occupancy by citalopram treatment in geriatric depression

Background: A single unprovoked seizure occurs in up to 10% of patients, but does not necessarily develop into epilepsy. It is unclear what determines the susceptibility to develop epilepsy. Although brain network changes have been ascertained in people with epilepsy, this field has not been studied in single seizure patients. Methods: Using 7T resting-state fMRI scanning, and co-registration watching a movie for naturalistic analysis of functional connectivity (Fc). Whole brain, Fc and Brodmann areas were analyzed using phase similarity measures and graph theory. Results: Ten patients with a single unprovoked seizure and fourteen age-and sex-matched healthy controls were recruited. Baseline characteristics were similar. Fc at baseline had no differences between groups. Movie-driven analysis did not show a significant difference overall regions but we observed significant differences in default mode and Visual association cortex as well as Dorsal posterior cingulate cortex (Dorsal PCC). Conclusions: Although no network connectivity differences were found between patients and controls, when movie-driven data was analyzed, differences were seen when comparing patients in the default mode network, visual association cortex, and dorsal posterior cingulate.

/pdf/p-036-exploring-changes-in-functional-connectivity-after-a-14p8ln7q.pdf

P.036 Exploring changes in functional connectivity after a first unprovoked seizure: an fMRI resting state and movie-driven data study

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Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder.

Serotonin transporter occupancy by citalopram treatment in geriatric depression

P.036 Exploring changes in functional connectivity after a first unprovoked seizure: an fMRI resting state and movie-driven data study