Compulsivity & Insulin Essay Flashcards
Compulsivity defined as
repetitive irresistable urge to perform a behaviour with loss of voluntary control over intense urge and diminished ability to inhibit thoughts or actions leading to habitual acts
Cross disorder trait
underlying phenotypically distinct psychiatric disorders that emerge throughout all stages of life
early life (autism)
late childhood (OCD)
addiction behaviours including SUD
typically manifests during adolescence
closely linked to ADHD
Autism
Autism characterised by deficits in social interaction and communication with stereotyped patterns of behaviour, interests and activities
repetitive motor behaviours
body movements
Comorbidity of ASD and ADHD
25-50% of ASD individuals present with ADHD symptoms and qualify for diagnosis
Increased risk of SUD and addictive behaviours
Mechanisms underlying compulsivity as cross-disorder trait
Cognitive, neural and genetic nature
Certain biomarkers underpinning association between compulsivity, impulsivity and addictive behaviours
The corticostriatal glutamate circuit is the primary brain region investigated in relation to compulsivity
with altered corticostriatal functional connectivity in OCD patients (Harrison et al. 2009)
More recently, abnormal corticostriatal-limbic functional connectivity in OCD patients during reward processing and steady state
signifys role of nucleus accumbens in compulsive behaviour (Jung et al. 2013)
NTS hypothesis underlying compulsivity
decreased serotonin in frontal cortical areas
serves as basis for SSRI medication despite 30-40% non response rate
overactivity of basal ganglia is likely cause of dysregulation in preventing certain actions or thoughts
dysregulation in frontal regions may also be a result of altered excitatory and inhibitory balance of glutamate and GABA respectively
in contrast to previous thinking
it is thought that perhaps compulsivity originates prior to obsession in the developmental trajectory of addictive behaviours
TACTICS (2012-2018)
preclinical and clinical research to identify neural, molecular and genetic factors involved in pathogenesis of compulsive behaviour
using a series of proof of concept studies
structural neuroimaging (MRI/DTI)
neurochemistry (MRS)
genetics (GWAS)
proteomics
behaviour
Bayesian machine learning tools
population for TACTICS
male and female pediatric clinical population and behavioural animal models to better understand the mechanisms related to glutamate dysfunction in frontostriatal circuits and remediation by early intervention with glutamate-based clinically used drugs, such as memantine
Animal models of compulsive behaviour used during the TACTICS project
provided valuable insights into the mechanisms underlying compulsivity as a cross-disorder trait
Compulsive lever pressing in signal attenuation mouse model of OCD
distinguishes compulsive behaviours from repetitive not compulsive
Adminstration of quinipirole
selective D2 and D3 receptor agonist induced compulsive checking behaviours in rats - implicating role of dopamine and basal ganglia in compulsivity
SLITKR5 deficient mice
demonstrate impaired corticostriatal circuitry and compulsivity in form of excessive barbering reversed withh fluoxetine SSRI implicating role of serotonin in compulsivity (shmelkov et al 2010) vet clinic - domesticated animals
reversal learning
useful assessment to measure compulsivity in animal models with reduced behavioural flexibility indicative of compulsive behaviours
VR in reversal learning
virtual reality environments used in young mice (Havenith et al 2019)
error detection in reversal learning indicative of ACC function
mice required to overcome learned avoidance of negative stimulus to acquire new association and OCD patients impaired reversal learning (Reminjinse et al 2016)
TALLYHO/JngJ and Insulin
