Compulsivity & Insulin Essay

Question 1

Compulsivity defined as

Answer 1

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

Question 2

Cross disorder trait

Answer 2

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

Question 3

Autism

Answer 3

Autism characterised by deficits in social interaction and communication with stereotyped patterns of behaviour, interests and activities

repetitive motor behaviours
body movements

Question 4

Comorbidity of ASD and ADHD

Answer 4

25-50% of ASD individuals present with ADHD symptoms and qualify for diagnosis

Increased risk of SUD and addictive behaviours

Question 5

Mechanisms underlying compulsivity as cross-disorder trait

Answer 5

Cognitive, neural and genetic nature
Certain biomarkers underpinning association between compulsivity, impulsivity and addictive behaviours

Question 6

The corticostriatal glutamate circuit is the primary brain region investigated in relation to compulsivity

Answer 6

with altered corticostriatal functional connectivity in OCD patients (Harrison et al. 2009)

Question 7

More recently, abnormal corticostriatal-limbic functional connectivity in OCD patients during reward processing and steady state

Answer 7

signifys role of nucleus accumbens in compulsive behaviour (Jung et al. 2013)

Question 8

NTS hypothesis underlying compulsivity

Answer 8

decreased serotonin in frontal cortical areas
serves as basis for SSRI medication despite 30-40% non response rate

Question 9

overactivity of basal ganglia is likely cause of dysregulation in preventing certain actions or thoughts

Answer 9

dysregulation in frontal regions may also be a result of altered excitatory and inhibitory balance of glutamate and GABA respectively

Question 10

in contrast to previous thinking

Answer 10

it is thought that perhaps compulsivity originates prior to obsession in the developmental trajectory of addictive behaviours

Question 11

TACTICS (2012-2018)

Answer 11

preclinical and clinical research to identify neural, molecular and genetic factors involved in pathogenesis of compulsive behaviour

Question 12

using a series of proof of concept studies

Answer 12

structural neuroimaging (MRI/DTI)
neurochemistry (MRS)
genetics (GWAS)
proteomics
behaviour
Bayesian machine learning tools

Question 13

population for TACTICS

Answer 13

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

Question 14

Animal models of compulsive behaviour used during the TACTICS project

Answer 14

provided valuable insights into the mechanisms underlying compulsivity as a cross-disorder trait

Question 15

Compulsive lever pressing in signal attenuation mouse model of OCD

Answer 15

distinguishes compulsive behaviours from repetitive not compulsive

Question 16

Adminstration of quinipirole

Answer 16

selective D2 and D3 receptor agonist induced compulsive checking behaviours in rats - implicating role of dopamine and basal ganglia in compulsivity

Question 17

SLITKR5 deficient mice

Answer 17

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

Question 18

reversal learning

Answer 18

useful assessment to measure compulsivity in animal models with reduced behavioural flexibility indicative of compulsive behaviours

Question 19

VR in reversal learning

Answer 19

virtual reality environments used in young mice (Havenith et al 2019)

Question 20

error detection in reversal learning indicative of ACC function

Answer 20

mice required to overcome learned avoidance of negative stimulus to acquire new association and OCD patients impaired reversal learning (Reminjinse et al 2016)

Question 21

TALLYHO/JngJ and Insulin