OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

Abstract

Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using 11C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n = 12) and matched healthy controls (HC; n = 12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability (11C-P943 BPND); however, the relationship between PPI and 11C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.

Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System

“…In addition, there is also evidence showing that the amygdala, accumbens nuclei, and other limbic systems contribute to the performance of ASR and PPI ( Frau et al, 2019 ). Considering the results we got from open field and PPI, where only male mutant mice displayed stress-related sensorimotor deficits, and taking in account that both tests involve the accumbens nucleus, amygdala nucleus, and mesolimbic dopamine system (that participate in many psychiatric disorders, such as schizophrenia, depression, obsessive–compulsive disorder, psychological substance-induced behavior, and so on), we hypothesized that sex hormone levels might affect the behaviors of Map2k5 +/– mutant mice where male mice was prone to manifest stress-related responses ( Pittenger et al, 2016 ; Khan and Powell, 2018 ; Liu et al, 2018 ; Bilel et al, 2019 ; Tapias-Espinosa et al, 2019 ).…”

Molecular and connectomic vulnerability shape cross-disorder cortical abnormalities

“…Receptor densities were estimated using PET tracer studies for a total of 18 receptors and transporters, across 9 neurotransmitter systems. These include dopamine (D 1 [59], D 2 [96,105,108,131], DAT [33]), norepinephrine (NET [8,22,31,95]), serotonin (5-HT 1A [98], 5-HT 1B [6,41,73,76,77,85,97,98], 5-HT 2A [9], 5-HT 4 [9], 5-HT 6 [87,88], 5-HTT [9]), acetylcholine (α 4 β 2 [6,52], M 1 [78], VAChT [1,7]), glutamate (mGluR 5 [32,106]), GABA (GABA A [80]), histamine (H 3 [42]), cannabinoid (CB 1 [34,79,81,93]), and opioid (MOR [60]). Volumetric PET images were registered to the MNI-ICBM 152 nonlinear 2009 (version c, asymmetric) template, aver-aged across participants within each study, then parcellated to 68 cortical regions.…”

Bidirectional Behavioral Selection in Mice: A Novel Pre-clinical Approach to Examining Compulsivity

“…Nest-building therefore encompasses sensorimotor, goaldirected and reward based neural mechanisms involving several neurotransmitter systems. Since, aberration of the abovementioned regions and neurotransmitter mechanisms has been documented in several studies investigating clinical populations (253)(254)(255)(256)(257)(258)(259), nest-building can be considered as a relevant and suitable behavioral phenotype to address some aspects of compulsivity in humans.…”